Cardiac Systolic Function Research Articles

Correlation between Blood Pressure and Left Ventricular Function in Neonates: A Retrospective Observational Study

Purpose: Ejection fraction, measured as the fraction of blood ejected from the ventricle in each heartbeat using M-mode echocardiography, serves as a primary indicator of left ventricular systolic function. This study explores the correlation between blood pressure and left ventricular systolic function in neonates using M-mode echocardiography.Methods: Neonates who underwent echocardiography in the neonatal intensive care unit between January 2011 and December 2020 were retrospectively studied.Results: Our analyses showed a significant association between ejection fraction and systolic blood pressure, but not with diastolic or mean blood pressure—both of which are more sensitive to hypotension. Ejection fraction was also not significantly associated with heart rate, urine output, or inotropic support in this study, suggesting that factors influencing urine output may not directly relate to ejection fraction. Additionally, we found that higher systolic blood pressure was correlated with advanced gestational age, the absence of patent ductus arteriosus, and no need for fentanyl administration. Notably, lower gestational age and lack of mechanical ventilation were both associated with increased hourly urine output, suggesting that developmental maturity and respiratory stability may influence renal function.Conclusion: Neonatal hypotension occurred secondary to decreased systolic cardiac function and peripheral vascular resistance. Neonatologists should carefully monitor the individual components of blood pressure and prescribe medications accordingly, considering that systolic blood pressure is correlated with ejection function.

EVALUATION OF THE RELATIONSHIP BETWEEN IRON LOAD, AGE, AND CARDIAC FUNCTION IN CHILDREN AND YOUNG ADULTS WITH THALASSEMIA MAJOR: A PULSED-WAVE DOPPLER AND TISSUE DOPPLER IMAGING STUDY

Objective: To determine the structural and functional cardiac differences in children and young adults with thalassemia major (TM) compared to healthy subjects using pulsed-wave Doppler and tissue Doppler imaging methods and determine the relationship between iron overload and these differences. Materials and Methods: We analyzed the data of pediatric and young adult TM patients (n = 44) aged 4–22 years and an age- and gender-matched control group (n = 40) in our hospital data system between Oct.01.2023 and Oct.01.2024. Height, weight, body mass index (BMI), systolic–diastolic blood pressure measurements, complete blood count, ferritin, cardiac T2* magnetic resonance imaging (MRI) values, and echocardiography results were recorded. In addition to comparisons between the two groups, correlation analysis was performed between ferritin–cardiac T2* MRI results and echocardiographic parameters and age in TM patients. Results: Our study showed growth retardation (low height standard deviation score (SDS), low weight SDS and low BMI SDS), dilatation of the left cavities (high left ventricular internal diameter end diastole (LVIDd)), increased left ventricular muscle mass (high left ventricular mass index (LVMI)), cardiac distinctive diastolic (restrictive pattern: left ventricular (LV) peak early diastolic flow (E)/peak late diastolic flow (A) and E/early diastolic myocardial peak flow (E') high), and subclinical systolic (LV peak systolic flow low and LV Tei index high) dysfunction. In addition, iron load (ferritin and cardiac T2* MRI) was correlated with LVMI, and cardiac diastolic and systolic function indicators. As age increased, ferritin value did not change, but cardiac T2* MRI value decreased and diastolic–systolic parameters worsened. Conclusion: Periodic cardiac T2* MRI and Doppler echocardiography examinations of patients with TM may detect subclinical myocardial dysfunction at an early stage, thus providing a window of opportunity for intervention.

ALPK2 prevents cardiac diastolic dysfunction in heart failure with preserved ejection fraction.

Protein phosphorylation, controlled by protein kinases, is central to regulating various pathophysiological processes, including cardiac systolic function. The dysregulation of protein kinase activity plays a significant role in the pathogenesis of cardiac systolic dysfunction. While cardiac contraction mechanisms are well documented, the mechanisms underlying cardiac diastole remain elusive. This gap persists owing to the historical focus on systolic dysfunction in heart failure research. Recently, heart failure with preserved ejection fraction (HFpEF), an age-related disease characterized by cardiac diastolic dysfunction, has emerged as a major public health concern. However, its underlying mechanism remains unclear. In this study, we investigated cardiac protein kinases by analyzing the gene expression of 518 protein kinases in human tissues. We identified alpha-kinase 2 (ALPK2) as a novel cardiac-specific atypical kinase and generated tamoxifen-inducible, cardiomyocyte-specific Alpk2-knockout mice and Alpk2-overexpressing mice. Alpk2 deficiency did not affect cardiac systolic dysfunction in the myocardial infarction model or the pressure-overload-induced heart failure model. Notably, cardiomyocyte-specific Alpk2 deficiency exacerbated cardiac diastolic dysfunction induced by aging and in the HFpEF model. Conversely, Alpk2 overexpression increased the phosphorylation of tropomyosin 1, a major regulator that binds myosin to actin, and mitigated cardiac stiffness in HFpEF. This study provides novel evidence that ALPK2 represents a potential therapeutic target for cardiac diastolic dysfunction in HFpEF and age-related cardiac impairments.

Reference intervals of two-dimensional speckle tracking–derived endocardial global longitudinal strain analysis in 132 healthy cats

IntroductionThe assessment of left ventricular myocardial deformation and function by two-dimensional speckle tracking–derived strain analysis is an established method in human cardiology. It also progressively gains recognition in veterinary cardiology in both dogs and cats. ObjectivesThe objectives of this study were to create reference intervals for two-dimensional speckle tracking echocardiography (STE)–derived endocardial global longitudinal strain (GLS) in a population of healthy adult cats of different breeds. Influences of heart rate, body weight, and age were investigated. AnimalsA total of 132 healthy, adult cats were included in this study. Materials and MethodsLeft apical two-, three-, and four-chamber views were obtained prospectively for GLS measurements using two-dimensional speckle tracking performed with cardiac performance analysis. Potential influence of body weight, heart rate, and age was analyzed, and the interobserver and intra-observer variability of the measurements was determined. ResultsEndocardial GLS values were not significantly influenced by body weight (P=0.102), heart rate (P=0.144), or age (P=0.075). A reference interval for GLS of −21.18% to −37.50% (±4.12) was determined. The interobserver and intra-observer variability showed excellent agreement. Discussion and ConclusionsTwo-dimensional STE is a feasible technique for the evaluation of cardiac myocardial deformation and systolic function in cats. Showing an excellent interobserver and intra-observer agreement, two-dimensional STE is a promising method for clinical analysis of cardiac deformation in cats.

Abstract 4123630: MRPL44 Plays an Important Role in Cardiac Hypertrophy and Function

Background: Mitochondrial ribosomal large subunit 44 (MRPL44) knockout mice were embryonic lethal, for which mutations are known to cause mitochondrial infantile cardiomyopathy and hypertrophic cardiomyopathy. However, it remains unknown how MRPL44 contributes to cardiac function and hypertrophy. Aims: Our aim is to investigate the effect of MRPL44 haploinsufficiency in mice. Methods: MRPL44 haploinsufficient (MRPL44 +/- ) mice were generated. Mineralocorticoid receptor-associated hypertension mice were induced in MRPL44 +/- and wild-type (WT, MRPL44 +/+ ) mice with subcutaneous infusion of aldosterone(Aldo) and 8% NaCl food for 4 weeks after uninephrectomy. Systolic blood pressure was measured by tail cuffs every week. WB, qPCR, cardiac echo, and histological examinations were performed. RNA sequencing analysis, electron microscopy examinations and mitochondrial activity assay were performed to find differences between MRPL44 +/- and MRPL44 +/+ mice. Results: MRPL44 haploinsufficient mice spontaneously developed left ventricular hypertrophy. Heart rate, blood pressure, and cardiac systolic function were normal in MRPL44 haploinsufficient mice. MRPL44 was decreased about to 70% in MRPL44 haploinsufficient mice and mitochondrial arrangement were impaired in electron microscopic analysis. After Aldo treatment, blood pressure elevation were similar, however, MRPL44 haploinsufficient mice developed left ventricular systolic dysfunction and dilation compared with MRPL44 +/+ mice. WB showed mitochondrial electron transport chain protein complex IV expression was significantly decreased. Furthermore, mitochondrial activity assay showed MRPL44 haploinsufficient mice had a significant reduction in complex IV activity, whereas complex I and II activity were similar to MRPL44 +/+ mice. RNA sequencing analysis showed the significant changes in the expression of ribosomal subunits coded by nucleus in addition to mitochondrial ribosomal subunits. These results indicate MRPL44 plays an important role in the cardiac function of mitochondrial electron transport chain protein complexes via the expression of ribosomal protein subunits coded by both nucleus and mitochondria. Conclusion: MRPL44 haploinsufficient mice spontaneously develop left ventricular hypertrophy and shows systolic dysfunction after aldosterone treatment accompanied with oxidative phosphorylation enzyme dysfunction.

High VExUS grades are linked to cardiac function in general ICU patients.

Even though initially considered as a new standard in systemic venous congestion assessment, the semi-quantitative Doppler ultrasound-based Venous Excess Ultrasound Grading System (VExUS) showed inconsistent associations with outcomes in general intensive care unit (ICU) patients. It is unclear why VExUS is so effective in predicting outcomes in some cohorts and not in others. The determinants of higher VExUS have not been studied in a general ICU cohort. The aim of this study was to determine the factors associated with higher VExUS (≥ 2) in a general ICU cohort. We performed a post-hoc analysis of a prospective, observational cohort, including adult patients within 24 hours of ICU admission and expected ICU length of stay longer than 2 days. Collected data included patients' hemodynamic status (including ultrasound evaluation) at several points in time: ICU admission, day 1, day 2, day 5, and the last day of ICU stay. We analyzed 514 hemodynamic evaluations in 145 patients. 96/514 (18.7%) had a VExUS grade ≥ 2. The univariable followed by multivariable mixed-effects logistic regression analyses only found a statistically significant association between VExUS ≥ 2 and right ventricle S wave (OR 0.85 (0.74;0.97), p = 0.02) and left ventricle E/A ratio (OR 2.34, 95% CI (1.27;4.33), p = 0.006). The current study has elucidated that higher VExUS is primarily associated with cardiac comorbidities and ultrasound parameters of left- and right-sided cardiac systolic and/or diastolic function in general ICU patients.

Klf9 is essential for cardiac mitochondrial homeostasis.

Mitochondrial dynamics and mitophagy are intimately linked physiological processes that are essential for cardiac homeostasis. Here we show that cardiac Krüppel-like factor 9 (Klf9) is dysregulated in human and rodent cardiomyopathy. Both global and cardiac-specific Klf9-deficient mice displayed hypertrophic cardiomyopathy. Klf9 knockout led to mitochondrial disarray and fragmentation, impairing mitochondrial respiratory function in cardiomyocytes. Furthermore, cardiac Klf9 deficiency inhibited mitophagy, thereby causing accumulation of dysfunctional mitochondria and acceleration of heart failure in response to angiotensin II treatment. In contrast, cardiac-specific Klf9 transgene improved cardiac systolic function. Mechanistically, Klf9 knockout decreased the expression of PGC-1α and its target genes involved in mitochondrial energy metabolism. Moreover, Klf9 controlled the expression of Mfn2, thereby regulating mitochondrial dynamics and mitophagy. Finally, adeno-associated virus-mediated Mfn2 rescue in Klf9-CKO hearts improved cardiac mitochondrial and systolic function. Thus, Klf9 integrates cardiac energy metabolism, mitochondrial dynamics and mitophagy. Modulating Klf9 activity may have therapeutic potential in the treatment of heart failure.

Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice.

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON. Western blot analyses of splenic immune checkpoint protein levels showed differential expression depending on sex and prevalent cardio-metabolic co-morbidities, suggesting T-cell exhaustion in both sexes on HFD + L-NAME, but more pronounced in males. In a sub-study with a similar setup, we tested cardiotoxic manifestations of ICI by treating mice with anti-PD-1 monoclonal antibody (ICI) for the last 2weeks of diet administration (n = 5-7). After 2weeks of ICI treatment, cardiac systolic functions significantly decreased in CON, but not in HFD + L-NAME groups of both sexes compared to baseline (before ICI administration). In conclusion, in this exploratory study using aged mice, we describe for the first time that ICI-related systolic dysfunction is diminished in both sexes when obesity and hypercholesterolemia are present, possibly due to obesity-related T-cell exhaustion.

Iatrogenic Cardiac Arrest During Thyroid Storm.

Thyroid storm is a life-threatening condition with often severe cardiac implications. Correct treatment choices can vary depending on underlying cardiac systolic function. We present a case of a 47-year-old male with untreated Grave's disease who presented with a thyroid storm. After propranolol administration, he experienced a cardiac arrest with the return of spontaneous circulation after cardiopulmonary resuscitation. Further evaluation revealed severe thyroid-induced cardiomyopathy with left ventricular ejection fraction of 15-20%, which had decreased from 60-65% over one year. The patient was discharged home on hospital day 8 after an unremarkable ischaemic work-up. He experienced a full cardiac systolic function recovery with an ejection fraction of 60-65% at the 90-day follow-up. Thyroid storm can present with overt or subclinical heart failure. Prompt evaluation of cardiac systolic function with a transthoracic echocardiogram before beta-blockade and the use of shorter-acting beta blockers can prevent devastating suppression of myocardial function. Despite being first-line therapy, beta blockers can be beneficial or devastating in thyroid storm patients depending on the presence of low cardiac output or high cardiac output heart failure.Clinical awareness, prompt echocardiography and the use of shorter half-life beta blockers can prevent rapid cardiac deterioration in thyroid storm patients.

Sestrin2 Attenuates Myocardial Endoplasmic Reticulum Stress and Cardiac Dysfunction During Ischemia/Reperfusion Injury.

Sesn2 (Sestrin2) is a stress-induced protein that provides protective effects during myocardial ischemia and reperfusion (I/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I/R injury. The goal of this study was to determine whether Sesn2-mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I/R. In vivo cardiac I/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild-type (WT) and cardiac-specific Sesn2 knockout(Sesn2cKO) mice. At 6 hours and 24 hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4-phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post-I/R. Hearts from Sesn2cKO mice displayed increased susceptibility to ER stress during I/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2cKO hearts compared with WT hearts during I/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin-induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2cKO mice. Sesn2 attenuates cardiac ER stress post-I/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I/R injury.

The impact of spinal anesthesia on cardiac function in euvolemic vascular surgery patients: insights from echocardiography and biomarkers.

Existing evidence of the effect of spinal anesthesia (SA) on cardiac systolic function is scarce and inconclusive. This study aimed to evaluate the effects induced by a single injection of SA for elective vascular surgery on left (LV) and right (RV) ventricular systolic performance using transthoracic echocardiography (TTE). A prospective study. Single-center study, university hospital. Adult patients undergoing elective vascular surgery with SA. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent TTE studies before and after SA induction for the assessment of indices reflective of LV and RV systolic function. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels. A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the study. The primary outcome was the difference before and after SA in LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE). In total population, LVEF significantly increased after SA 53.07% [16.51]vs 53.86% [13.28]; p < 0.001). End-systolic volume (ESV, 69.50 [51.50] vs. 65.00 [29.50] ml; p < 0.001) decreased while stroke volume (SV) insignificantly increased (70.51 ± 16.70 vs. 73.00 ± 18.76ml; p = 0.131) during SA. TAPSE remained unchanged (2.23 [0.56] vs. 2.25 [0.69] mm; p = 0.558). In patients with impaired compared to those with preserved LV systolic function, the changes evidenced in LVEF (7.49 ± 4.15 vs. 0.59 ± 2.79; p < 0.001), ESV (-18.13 ± 18.20 vs-1.53 ± 9.09; p < 0.001) and SV (8.71 ± 11.96 vs-1.43 ± 11.89; p = 0.002) were greater. This study provides evidence that SA in patients undergoing elective vascular surgery improved LV systolic function, while changes in RV systolic function are minimal.

Tipping the scale: Effects of physical activity and body composition on cardiac parameters in postmenopausal females.

The risk of cardiovascular disease increases significantly after menopause. We sought to assess the impact of different activity levels on cardiac structure and function in postmenopausal women. We grouped age-similar, postmenopausal women by self-reported physical activity levels over two decades. The study involved 34 women (age 61 ± 1 years; 11 ± 2 postmenopausal years; body mass index 23 ± 3 kg/m2) categorized into three activity tiers: sedentary (SED; ≤1 h exercise weekly; n = 9); moderately active (MOD; ≥2 ≤6 h low/moderate intensity exercise weekly; n = 11) and highly active (HIGH; >4 h of moderate/high intensity exercise weekly; n = 14). Maximum oxygen uptake (VO2max) differed significantly (p < 0.05) between the groups (24.9 ± 5.8; 30.5 ± 5.8; 38.4 ± 4.4 mL O2/kg/min; SED, MOD and HIGH respectively). Conversely, there were no differences (p > 0.05) in height, Total fat-free mass, body surface area or in echocardiographic measures of left ventricular (LV) morphology, systolic function, diastolic function and right ventricular function. Contrary to our hypothesis, these findings reveal that marked differences in activity level and VO2max are not reflected in measures of LV morphology or echocardiographic indicators of cardiac diastolic or systolic function in postmenopausal women of similar body size.

Sinomenine hydrochloride alleviates autoimmune myocarditis via suppressing Th1 cell induced-M1 macrophage pyroptosis

Abstract Background Myocarditis is typical of the complex inflammatory response in the heart with high morbidity and mortality, accompanied by tissue damage and cardiac fibrosis. Previous studies have demonstrated that CD4+ T cells are crucial to the cardiac autoimmunity of myocarditis, but the role of different CD4+ T cell subsets remains unclear. Recently, sinomenine hydrochloride, a natural compound from the traditional Chinese herb Sinomenium acutum, is reported to inhibit T cell proliferation in some systemic autoimmune diseases such as rheumatoid arthritis. Given that autoimmune myocarditis is an organ-specific autoimmune disease, the effect of sinomenine hydrochloride on autoimmune myocarditis demands further study. Purpose This study aims to elucidate the role of CD4+ T-helper 1 (Th1) cells in regulating inflammatory cell death in autoimmune myocarditis and investigate the pharmacological effect of sinomenine hydrochloride on CD4+ Th1 cells and autoimmune myocarditis. Methods Male Balb/c mice were immunized with myosin heavy chain-α peptides to establish the experimental autoimmune myocarditis (EAM) model, followed by the treatments with sinomenine hydrochloride by gavage. Tohoku Hospital Pediatrics-1 (THP-1) cell line and murine T cells were used for in vitro experiments. Results In the acute phase of EAM, we observed plenty of CD4+ T cells infiltrating the heart tissue. RNA sequencing revealed that among the genes encoding typical transcription factors of CD4+ T cell subset, only Tbx21 and Stat4, both representing Th1 cells, were upregulated, which consisted with immunofluorescence staining. Further studies indicated that Th1 cells not only mediated classical activated macrophage (M1 macrophage) polarization by secreting interferon-γ (IFN-γ) but also associated with pro-inflammatory macrophage pyroptosis in the EAM, with the cleavage of gasdermin D (GSDMD), caspase-1 and IL-1β. Subsequent in vitro experiments confirmed that IFN-γ could dramatically promote macrophage pyroptosis combined with ATP, leading to the release of IL-1β and IL-18(Figure 1). To find an effective method for Th1 cell suppression and myocarditis remission, we identified that sinomenine hydrochloride impeded Th1 cell activation, differentiation and proliferation in vitro. Furthermore, sinomenine hydrochloride inhibited Th1 cell infiltration and M1 macrophage pyroptosis in the EAM heart, In the chronic phase, cardiac remodeling and fibrosis were suppressed, and cardiac systolic function was significantly improved in the treatment group (Figure 2). Conclusion Our study demonstrates that Th1 cells-induced M1 macrophage pyroptosis is an essential pathogenic mechanism of EAM. Sinomenine hydrochloride can alleviate the severity and progression of EAM, which may become a novel therapeutic strategy for treating myocarditis.Figure 1Figure 2

MRPL44 haploinsufficient mouse spontaneously develops hypertrophic cardiomyopathy and shows systolic dysfunction after aldosterone treatment

Abstract Introduction It has been recently reported there are big differences in pathophysiological and molecular phenotypes in mouse and human hypertrophic cardiomyopathy. These differences are observed all in terms of myocyte redox, mitochondrial number and respiration, mitochondrial reactive oxygen species generation and Ca2+ handling. Therefore we should search for molecules to be able to induce similar phenotype and molecular signaling both in mice and human. Mitochondrial ribosomal large subunit 44 (MRPL44) knockout mice were embryonic lethal, for which mutations are known to cause mitochondrial infantile cardiomyopathy and hypertrophic cardiomyopathy. Purpose Our purpose is to investigate the effect of MRPL44 haploinsufficiency in mice. Methods MRPL44 haploinsufficient (MRPL44+/-) mice were generated. Mineralocorticoid receptor-associated hypertension mice were induced in MRPL44+/- and wild-type (WT, MRPL44+/+) mice with subcutaneous infusion of aldosterone(Aldo) and 8% NaCl food for 4 weeks after uninephrectomy. Systolic blood pressure was measured by tail cuffs every week. WB, qPCR, cardiac echo, and histological examinations were performed. RNA sequencing analysis, electron microscopy examinations and mitochondrial activity assay were performed to find differences between MRPL44+/- and MRPL44+/+ mice. Results MRPL44 haploinsufficient mice spontaneously developed left ventricular hypertrophy in 6 weeks old. Heart rate, blood pressure, and cardiac systolic function were normal in MRPL44 haploinsufficient mice. MRPL44 was decreased about to 70% in MRPL44 haploinsufficient mice and mitochondrial arrangement were impaired in electron microscopic analysis. After Aldo treatment, blood pressure elevation were similar, however, MRPL44 haploinsufficient mice developed left ventricular systolic dysfunction and dilation compared with MRPL44+/+ mice. WB showed mitochondrial electron transport chain protein complex IV expression was significantly decreased. Furthermore, mitochondrial activity assay showed MRPL44 haploinsufficient mice had a significant reduction in complex IV activity, whereas complex I and II activity were similar to MRPL44+/+ mice. RNA sequencing analysis showed the significant changes in the expression of ribosomal subunits coded by nucleus in addition to mitochondrial ribosomal subunits. These results indicate MRPL44 plays an important role in the cardiac function of mitochondrial electron transport chain protein complexes via the expression of ribosomal protein subunits coded by both nucleus and mitochondria. Conclusions MRPL44 haploinsufficient mice spontaneously develop left ventricular hypertrophy and shows systolic dysfunction after aldosterone treatment accompanied with oxidative phosphorylation enzyme dysfunction.

Left ventricular volume as a predictor of exercise capacity and functional independence in individuals with preserved ejection fraction

Abstract Background Cardiorespiratory fitness (CRF) is vital for independent living and is a powerful prognostic marker. Increased left ventricular (LV) volume has been linked with high CRF in athletes, but its utility as a diagnostic marker of low CRF across the entire health-disease continuum has yet to be tested. Methods This multi-center international cohort from Australia and Belgium examined the relationship between ventricular size on resting echocardiography and CRF (peakVO2 from cardiopulmonary exercise testing [CPET] or CPET with simultaneous echocardiography) in individuals with preserved LV ejection fraction (≥50%). LV end-diastolic volume (LVEDV) and LVEDV indexed to body surface area (LVEDVi) were tested as predictors of very low CRF (CRF associated with functional disability - peakVO2 &amp;lt; 1100ml or &amp;lt;18 ml/kg/min) and compared against other candidate measures of systolic and diastolic cardiac function that have been associated with heart disease. Thresholds for absolute and indexed LVEDV which best distinguished between lower and higher CRF status were identified. Results 2876 individuals (251 healthy non-athletes, 309 elite endurance athletes, 1969 individuals with unexplained dyspnea, 347 individuals with heart failure with preserved ejection fraction) were included. For the entire cohort, LVEDV had the strongest univariate association with peakVO2 (R2 = 0.45, standardized [std] β 0.67, p&amp;lt; 0.001) and, remained the strongest independent predictor of peakVO2 after adjusting for age, sex and body mass index (std β 0.44, p &amp;lt; 0.001). The relationship between LVEDV and VO2peak differed based on health/disease status (Figure 1). LVEDV demonstrated the greatest diagnostic capability in identifying functional disability (LVEDV AUC 0.72; LVEDVi AUC 0.71, Figure 2), outperforming ejection fraction, diastolic velocities, atrial volumes and pulmonary artery pressure estimates. The probability of achieving a peak VO2 below the threshold required for functional independence was highest for smaller ventricular volumes with LVEDV and LVEDVi of 88ml and 57 ml/m2 proving the optimal cut-points, respectively. Conclusions A small LVEDV is associated with a higher probability of poor exercise capacity, failure to achieve the peak VO2 required for functional independence and is the strongest independent echocardiographic predictor of CRF across the health-disease continuum.Figure 1.Ventricular Size and CRFFigure 2.Predictors of CRF status

ND15, subunit of the electron transport chain protein-complex I, age-dependently worsens cardiac performance in Drosophila melanogaster

Abstract Introduction In the natural aging process of the heart, aside others, mitochondrial dysfunction is an essential driver for the development of reduced cardiac performance. Previous analysis of protein expression levels in cardiomyocytes of aged mice and have found aberrancies in subunits of the mitochondrial Complexes I – IV of the electron transport chain. Especially, the complex I subunit ND15 was highly downregulated. To elucidate the functional effects of this gene on the cardiac performance, we generated cardiomyocyte specific ND15 knock-downs in Drosophila melanogaster. Methods We generated Drosophila with heart-specific (+/+; Hand4.2-GAL4/UAS-ND15; tdtK/+) (ND15-KD)knockdown of ND15 using the UAS/GAL4 system. The flies' cardiomyocytes endogenously express tdTomato, facilitating fluorescence-based live imaging of the heart by high-resolution video fluorescence microscopy. The recorded data was processed using a R-Script, resulting in Results We compared wild type (WT) flies to ND15-KD flies at age 3 weeks(young) and 7 weeks(old). Knockdown of ND15 resulted in impaired cardiac function. Most parameters deteriorated in aged flies in comparison to young flies. The heart frequency was significantly reduced (WT:6 beats/s – KD:4 beats/s – p&amp;lt;0.0001) in the 7 weeks old group, end-diastolic diameter of the heart tube increased significantly in 3 weeks old ND15KD flies compared to controls(WT:65µm – KD:74µm p&amp;lt;0,0001), resulting in a dilated heart tube Interestingly enough, this dilation in ND15-KD disappeared in 7 weeks old flies. The fractional shortening was significantly decreased in young(WT:33,5% - KD:30% p&amp;lt;0,01) and deteriorated in old flies (WT:35% - KD:22% p&amp;lt;0,0001), indicating a reduced contraction capability. For both 3 weeks and 7 weeks old groups, the heart-rate adjusted interbeat interval variance (WT:22% -KD: 40% p&amp;lt;0,0001) as well as the time of no cardiac action (WT: 22% - KD: 35% p&amp;lt;0,0001) increased and showed significant irregularities. The duration of systole and diastole combined also exhibited arrhythmic patterns (WT:15% - KD:20.5% p&amp;lt;0,0001). A general arrhythmia index (AI) increased significantly (WT: 0.25 – KD:0.5 p&amp;lt;0,0001) These arrhythmia parameters emphasize the arrhythmogenic potential of the ND15-knockdown. The relative relaxation capabilities drastically worsened with age, displaying a diastolic dysfunction in the 7 weeks old group. At half-time relaxation, the WT was at 60% relaxation, ND15KD at 46%). Conclusion This study demonstrates that heart-specific deletion of ND15 results in a marked impairment of systolic and diastolic cardiac function in Drosophila accompanied by pro-arrhythmogenic actions. We could identify ND15 as a new mitochondrial molecular target for the maintenance of regular cardiac function and rhythmicity, especially with increasing age. Further mechanistic studies and translation to mammalian organisms are ongoing.

Left ventricular absolute myocardial work measured by cardiovascular magnetic resonance: a proof-of-concept

Abstract Background Myocardial Work Index (MWI) is a load-independent and non-invasive method for assessing cardiac systolic function [1]. However, MWI does not directly measure absolute myocardial work (AMW), since it does not consider the effect of variations in left ventricular (LV) wall thickness and regional wall curvature. Therefore, a direct comparison of MWI results may be difficult. Cardiovascular magnetic resonance (CMR) is the gold standard for assessing the LV geometry and therefore can be used to directly measure the AMW by calculating the area of the stress-strain curve. Purpose This study aims to measure and compare CMR-based AMW in three groups with different work profiles: healthy subjects, patients with ST-elevation myocardial infarction (STEMI), and patients with severe aortic valve stenosis (AS). Additionally, it aims to compare AMW with strain to provide additional insights into remodelling. Methods A total of 78 participants were included in our study; 38 healthy subjects from the CENS study [2], 19 STEMI patients 3-7 days post-PCI from the ASSAIL study [3], and 21 patients with AS scheduled for operation. Collected data were not adjusted for age or sex. Stress was estimated using Laplace’s equation [4]. Intra-ventricular pressure was calculated from brachial cuff pressure as previously described [5]. Mid-ventricular circumferential strain was calculated using CMR-based tissue phase mapping [4]. AMW was calculated both as Myocardial Work per unit endocardial Surface (MWS, in J/m^2) and per unit Mass (MWM, in mJ/g), both serving as measurements of global circumferential systolic function. Results Mean circumferential strain did not differ significantly between the AS and the healthy groups (p=0.37), but it was significantly lower in the STEMI group compared to the healthy group (p&amp;lt;0.001). MWS was significantly higher in the AS group (p&amp;lt;0.001) and lower in the STEMI group (p&amp;lt;0.001) compared the healthy group. This suggests that each unit of endocardial surface in the myocardium performed, on average, more work in the AS group and less work in the STEMI group relative to the healthy group. MWM was not significantly different between the AS and the healthy group (p=0.74), while in the STEMI group, it was significantly lower (p=0.001) than in healthy subjects. Conclusion Our results indicate that in patients with AS, the myocardium did more work per unit surface, while each gram of the myocardium did the same amount of work. This is likely due to concentric hypertrophy and the increase of afterload. In contrast, in patients with STEMI, the myocardium did, on average, less work per unit surface and per mass. This is expected due to the direct loss of mechanical function in the infarcted myocardium. Our results indicate that AMW enhances traditional strain analysis, improves myocardial function evaluation, and may provide deeper insight into myocardial remodeling in diverse cardiac conditions.

Cardiac Fatigue in Male Athletes with Exercise-Induced Pulmonary Impairments After a Very Long-Distance Triathlon.

Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar-capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions. Sixty trained male triathletes (age 39 ± 9years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV1), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DMCO/alveolar volume) were compared with those without these dysfunctions. The race lasted 14h 20min ± 1h 26min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E', which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (- 26 ± 13 versus - 15 ± 9%, P = 0.001) and positively correlated with DMCO/alveolar volume reduction. After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar-capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise.

Assessment of fetal cardiac function in pregnant women with anemia: prospective case-control study.

To compare fetal cardiac function in pregnant women with iron deficiency anemia (IDA) vs healthy pregnant controls. This was a single-center, prospective, case-control study conducted in a tertiary hospital between November 2022 and September 2023. Women diagnosed with IDA who attended as outpatients at the pregnancy follow-up clinic at 30-34 weeks' gestation or who were hospitalized for intravenous iron treatment owing to profound anemia were included. The control group consisted of randomly selected gestational-age-matched pregnant women with no obstetric complications or comorbidities and who did not have anemia. Patients underwent two-dimensional imaging, followed by pulsed-wave Doppler and M-mode and tissue Doppler imaging (TDI) to evaluate fetal cardiac function. A fetal cardiac score was calculated using systolic, diastolic and global hemodynamic function parameters, and was compared between patients with IDA and those without. The fetal cardiac score was also assessed according to the severity of anemia in the IDA group. A total of 150 patients, comprising 50 patients with IDA and 100 healthy pregnant women at 30-34 weeks' gestation, were included in the study. Of the patients with IDA, 20 had mild, 18 had moderate and 12 had severe anemia. The fetal myocardial performance index and isovolumetric relaxation time were significantly higher in the IDA group compared with the control group (P < 0.0001 for both), while isovolumetric contraction time was similar. Among the fetal tricuspid and mitral valve diastolic parameters, the E, A and E/A values were significantly lower in the IDA group (P < 0.05 for all). Mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursions were significantly lower in the IDA group (P < 0.05 for both). The IDA group also had significantly lower values for the TDI parameters mitral and tricuspid E', A', S' and E'/A' ratio and a significantly higher E/E' ratio (P < 0.05 for all). Among the IDA subgroups, a significant decrease was observed in the tricuspid and mitral A, E and E/A ratio in fetuses whose mothers had severe anemia (P = 0.001). M-mode Doppler analysis revealed significantly lower fetal TAPSE and MAPSE in the patient group with severe maternal anemia (P = 0.001 for both). According to the subgroup comparison of TDI findings, the fetuses of mothers with severe anemia had significantly lower tricuspid and mitral E', A', S' and E'/A' ratio values and a significantly higher E/E' ratio (P < 0.05 for all). The fetal cardiac score was significantly higher in the maternal IDA group compared with the control group (P < 0.001). A significant negative correlation was found between maternal hemoglobin level and fetal cardiac score (P < 0.001). We observed differences in fetal systolic and diastolic cardiac function in pregnancies with maternal IDA. Fetal cardiac function was affected more among patients with severe anemia. This study found an increased E/E' ratio in the fetuses of pregnant women with IDA, suggesting decreased fetal heart maturation. Prenatal fetal cardiac evaluation, especially in women with severe anemia, can facilitate a more seamless transition to the postnatal period for these newborns. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Causes and Diagnostic Significance of Coughing in Dogs with Endocardiosis

Introduction. Endocardiosis is the most widespread acquired cardiac disease in small dog breeds, characterised by the valvular degeneration leading to mitral insufficiency. Progression of mitral regurgitation leads to cardiac remodeling, increased left ventricular filling pressures, pulmonary hypertension and, eventually, myocardial dysfunction. Decreased exercise tolerance, dyspnea, anorexia, and coughing are the most often reported signs in dogs with endocardiosis. Coughing is often reported as the primary clinical sign of congestive heart failure in dogs with endocardiosis. The concomitant respiratory tract disease and compression of the left mainstem bronchus by the giant left atrium have also been suggested as the potential causes of coughing in these patients. However, the absence of relief from cough in dogs with endocardiosis when treated with calcium sensitizers and the registered improvement in systolic cardiac function makes doubtful the cardiogenic nature of coughing in endocardiosis. In other words, the clinical and diagnostic significance of coughing in dogs with endocardiosis has not been sufficiently studied. The aim of the present research is to determine the frequency of cough incidence in dogs with endocardiosis and to establish the pathognomonic nature of this symptom in endocardiosis, its clinical significance.Materials and Methods. The medical records of 49 dogs that have attended to the veterinary clinics of the “Vita” network (Rostov region) for cardiological examination in the period from September 1, 2021 to July 31, 2024 were analysed. The research was carried out using the following equipment: premium ultrasound scanner with improved image quality on the ZST+ Mindray Vetus 9 platform, Maxivet 400 veterinary X-ray digital DR system, and Poli-Spectrum–8/V computerassisted electrocardiograph.Results. The research allowed us to find out the following: although the cardiomegaly and the increase in the size of the left ventricle in endocardiosis can aggravate and intensify the clinical manifestation of coughing in dogs with degenerative diseases of the upper respiratory tract, they are not the necessary condition for the occurrence of coughing. Coughing in dogs with endocardiosis should be considered as a clinical sign of the concomitant inflammatory or degenerative disease of the upper respiratory tract, which should be taken into account in therapy and in the attempt to improve the quality of life of these animals.Discussion and Conclusion. We have found that only 57% of the dogs with clinically evident endocardiosis suffer from coughing, whereas it does not have the uniform nature. In dogs with cardiogenic pulmonary edema, a cough is not loud, is usually acute and is associated with the flow of fluid into the medium and large-sized bronchi. The chronic loud, hoarse cough, intensifying in the morning, is typical for dogs with endocardiosis and chronic bronchitis: these animals at the same time have the non-specific inflammatory lesion of the bronchial tree and lesion of the mitral valves. Most severe coughing, with the characteristic loud sound, is observed in dogs suffering from the elements of the upper respiratory tract collapse and cardiomegaly due to endocardiosis.