CMR provides comparable measurements of diastolic function as echocardiography.

Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p < 0.0001). The trans-mitral inflow parameters correlated well between the two modalities (E, r = 0.78; A, r = 0.90; E/A, r = 0.82; all p < 0.0001) while the remaining diastolic parameters showed moderate correlation (e', r = 0.64; E/e', r = 0.54; left atrial volume index (LAVi), r = 0.61; all p < 0.0001). Classification of LV diastolic function by CMR showed good concordance with standardized grades established for TTE. CMR-based LV diastolic function may be integrated in routine clinical practice.Name of the registry: Technical Development of Cardiovascular Magnetic Resonance Imaging. Trial registration number: NCT00027170. Date of registration: November 26, 2001. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT00027170.

Acute effect of ultramarathon on systolic and diastolic cardiac function: Systematic review and meta-analysis.

BACKGROUND: Ultramarathon running poses physiological challenges, impacting cardiac function. This systematic review and meta-analysis explore the acute effects of single-stage ultramarathon running on cardiac function. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were followed. Searches covered Medline, Embase, CINAHL, SPORTDiscus, Web of Science, Central Cochrane, and Scopus. Random effects meta-analyses assessed left ventricular (LV) and right ventricular (RV) variables, expressed as mean differences (MD) with 95% confidence intervals (CI). RESULTS: Among 6972 studies, 17 were included. Post-ultramarathon reductions were found in LV end-diastolic diameter (LVEDD) (-1.24; 95% CI = -1.77, -0.71 mm), LV end-diastolic volume (LVEDV) (-9.92; 95% CI = -15.25, -4.60 ml), LV stroke volume (LVSV) (-8.96 ml, 95% CI -13.20, -4.72 ml), LV ejection fraction (LVEF) (-3.71; 95% CI = -5.21, -2.22%), LV global longitudinal strain (LVGLS) (-1.48; 95% CI = -2.21, -0.76%), E/A (-0.30; 95% CI = -0.38, -0.22 cm/s), .E' (-1.35 cm/s, 95% CI -1.91, -0.79 cm/s), RV fractional area change (RVFAC) (-3.34, 95% CI = -5.84, -0.84%), tricuspid annular plane systolic excursion (TAPSE) (-0.12, 95% CI = -0.22, -0.02 cm), RV global longitudinal strain (RVGLS) (-1.73, 95% CI = -2.87, -0.59%), with increases in RV end-diastolic area (RVEDA) (1.89, 95% CI = 0.63, 3.14 cm2), RV Peak A' (1.32 cm/s, 95% CI 0.20, 2.44), and heart rate (18.24, 95% CI = 15.16, 21.32). No significant differences were observed in LV end-systolic diameter (LVESD), LV end-systolic volume (LVESV), RV end-diastolic diameter (RVEDD), RV Peak E', and RV Peak S'. CONCLUSIONS: Evidence suggests immediate impairment of systolic and diastolic cardiac function post-ultramarathon running.

Sodium overload during postnatal phases impairs diastolic function and exacerbates reperfusion arrhythmias in adult rats.

Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood. Male 21-day-old Wistar rats were treated for 60 days with hypertonic saline solution (NaCl; 0.3M; experimental group) or tap water (control group). Subsequently, both groups were maintained on a normal sodium diet for 30 days. Subsequently, the rats were euthanized, and their hearts were isolated and perfused according to the Langendorff technique. After 30 min of the basal period, the hearts were subjected to 20 min of anoxia, followed by 20 min of reperfusion. The basal contractile function was unaffected by HSD. However, HSD elevated the left ventricular end-diastolic pressure during reperfusion (23.1 ± 5.2 mmHg vs. 11.6 ± 1.4 mmHg; p < 0.05) and increased ectopic incidence period during reperfusion (208.8 ± 32.9s vs. 75.0 ± 7.8s; p < 0.05). In conclusion, sodium overload compromises cardiac function after reperfusion events, diminishes ventricular relaxation, and increases the severity of arrhythmias, suggesting a possible arrhythmogenic effect of HSD in the postnatal phases.

Effect of the early diastolic blood pressure response to the head-up tilt test on the recurrence of benign paroxysmal positional vertigo.

BACKGROUND: Otolith organ acts complementarily with the autonomic nervous system to maintain blood pressure. However, the effect of blood pressure variability in the autonomic nervous system on otolith organ has not yet been determined. This study aimed to verify the hypothesis that blood pressure variability in the autonomic nervous system affects the recurrence of benign paroxysmal positional vertigo (BPPV), which is the most common disease of the vestibular organs, by using the head-up tilt test (HUTT). METHODS: This study included 432 patients diagnosed with idiopathic BPPV. The follow-up period for all patients was 12 months. Age, sex, hypertension, diabetes and recurrence were analyzed. The HUTT parameters were divided into a group of patients whose average diastolic blood pressure increased in the upright position compared to supine position during the HUTT (DBP1) and a group of patients whose average diastolic blood pressure decreased in the upright position compared to supine position during the HUTT (DBP2). Model selection, general loglinear analysis, and logit loglinear analysis were performed using a hierarchically progressing loglinear analysis. RESULTS: In summary, the group with increased average diastolic blood pressure (DBP1) showed a higher tendency for BPPV recurrence compared to the group with decreased diastolic blood pressure (DBP2) in the upright position during the HUTT, although the difference was not statistically significant (p = 0.080). However, in males, the DBP1 group demonstrated a significantly higher recurrence rate of BPPV than the DBP2 group during the HUTT (95% CI, -20.021 to -16.200; p < 0.001). CONCLUSIONS: It is presumed that poor autonomic nervous system response through vestibulosympathetic reflex maintains elevated diastolic blood pressure in the upright position during the HUTT. This variability is assumed to affect the recurrence of BPPV.

Speckle-Tracking: Incremental Role in Diastolic Assessment of Pediatric Patients with Chronic Kidney Disease. / Strain do Átrio Esquerdo pela Técnica de Speckle-Tracking: Contribuição para a Avaliação da Função Diastólica em Pacientes Pediátricos com Doença Renal Crônica.

BACKGROUND: Cardiovascular complications are the leading cause of mortality in pediatric patients with chronic kidney disease (CKD). Echocardiographic assessment of diastolic function in CKD has been limited to spectral and tissue Doppler imaging, known to be less reliable techniques in pediatrics. Two-dimensional Speckle tracking echocardiography (2DST) derived left atrial (LA) strain has recently been confirmed as a robust measure of diastolic function. OBJECTIVES: To investigate LA strain role in diastolic assessment of children at different stages of CKD. METHODS: From February 2019 to July 2022, 55 CKD patients without cardiovascular symptoms and 55 controls were evaluated by standard and 2DST echocardiograms. The level of significance was set at 5% (p<0.05). RESULTS: Patients and controls had similar age [9.78 (0.89 - 17.54) vs. 10.72 (1.03 -18,44) years; p = 0.41] and gender (36M:19F vs. 34M:21F; p=0.84). There were 25 non-dialysis patients and 30 dialysis patients. Left ventricular ejection fraction was ≥ 55% in all of them. Comparing CKD and controls, LA reservoir strain was lower (48.22±10.62% vs. 58.52±10.70%) and LA stiffness index was higher [0.14 (0.08-0.48)%-1 vs. 0.11 (0.06-0.23) %-1]; p<0.0001. LV hypertrophy was associated with lower LA reservoir strain (42.05±8.74% vs. 52.99±9.52%), higher LA stiffness [0.23(0.11 - 0.48)%-1 vs. 0.13 (0.08-0.23) %-1 and filling indexes (2.39±0.63 cm/s x %-1 vs. 1.74±0.47 cm/s x %-1; p<0.0001. Uncontrolled hypertension was associated with lower LA reservoir strain (41.9±10.6% vs. 50.6±9.7; p=0.005). CONCLUSIONS: LA strain proved to be a feasible tool in the assessment of pediatric CKD patients and was associated with known cardiovascular risk factors.

FUNDAMENTO: As complicações cardiovasculares são a principal causa de morte em pacientes pediátricos com doença renal crônica (DRC). A avaliação ecocardiográfica da função diastólica na DRC tem se limitado à avaliação espectral por Doppler espectral e por Doppler tecidual, técnicas sabidamente menos confiáveis na pediatria. O strain do átrio esquerdo (AE) pela técnica do speckle tracking bidimensional (2DST) foi recentemente confirmada como uma medida robusta da função diastólica. OBJETIVOS: Investigar o papel do strain do AE na avaliação da função diastólica de crianças em diferentes estágios da DRC. MÉTODOS: De fevereiro de 2019 a julho de 2022, 55 pacientes com DRC sem sintomas cardiovasculares e 55 controles foram avaliados por ecocardiografia convencional e por ecocardiografia com 2DST. O nível de significância adotado foi de 5% (p < 0,05). RESULTADOS: Pacientes e controles tinham idade similares [9,78 (0,89 ­ 17,54) vs. 10,72 (1,03 ­18,44) anos; p = 0,41] e sexo (36M:19F vs. 34M:21F; p = 0,84) similares. Havia 25 pacientes não dialíticos e 30 pacientes dialíticos. A fração de ejeção do ventrículo esquerdo foi ≥ 55% em todos. Em comparação aos controles, os pacientes com DRC apresentaram strain de reservatório mais baixo (48,22±10,62% vs. 58,52±10,70%) e índice de rigidez do AE mais alto [0,14 (0,08­0,48)%-1 vs. 0,11 (0,06­0,23) %-1]; p<0,0001. A hipertrofia ventricular esquerda associou-se com um strain de reservatório mais baixo (42,05±8,74% vs. 52,99±9,52%), e valores mais altos de índice de rigidez [0,23 (0,11 ­ 0,48)%-1 vs. 0,13 (0,08­0,23) %-1 e de índice de enchimento do AE (2,39±0,63 cm/s x %-1 vs. 1,74±0,47 cm/s x %-1; p<0,0001). Hipertensão não controlada associou-se com strain de reservatório do AE mais baixo (41,9±10,6% vs. 50,6±9,7; p=0,005). CONCLUSÃO: O strain do AE mostrou-se uma ferramenta útil na avaliação de pacientes pediátricos com DRC e associado com fatores de risco cardiovasculares conhecidos.

Structural and functional cardiac parameters across occupations: a cross-sectional study in differing work environments.

Previous investigations have highlighted notable variations in cardiovascular risk indicators associated with various professional categories. However, only a few studies have examined structural and functional cardiac parameters using echocardiography within distinct occupational groups. Hence, this study endeavored to assess cardiac structural and functional parameters in three additional occupations: firefighters (FFs), police officers (POs), and office workers (OWs). This prospective study encompassed 197 male participants (97 FFs, 54 POs, and 46 OWs) from Germany. All participants underwent 2D and Doppler echocardiography in resting conditions; standard parasternal and apical axis views were employed to evaluate structural (diastolic and systolic) and functional (systolic and diastolic function, and strain) cardiac parameters. All three occupational groups exhibited a tendency towards septal hypertrophy. Notably, OWs exhibited the largest diastolic interventricular septum diameter (IVSd), at 1.33 ± 0.25 cm. IVSd significantly varied between POs and OWs (p = 0.000) and between POs and FFs (p = 0.025). Additionally, during diastole a substantially larger left ventricular posterior wall diameter (LVPWd) was observed in OWs compared to FFs (p = 0.001) and POs (p = 0.013). The left ventricular diastolic cavity diameter (LVIDd) and the left ventricular systolic cavity diameter (LVIDs) were significantly higher in POs than they were in FFs (LVIDd: p = 0.001; LVIDs: p = 0.009), and the LVIDd was notably higher in FFs (p = 0.015) and POs compared to OWs (p = 0.000). FFs exhibited significantly better diastolic function, indicated by higher diastolic peak velocity ratios (MV E/A ratio) and E/E' ratios, compared to POs (E/A ratio: p = 0.025; E/E' ratio: p = 0.014). No significant difference in diastolic performance was found between OWs and FFs. Significantly higher E'(lateral) values were noted in POs compared to FFs (p = 0.003) and OWs (p = 0.004). Ejection fraction did not significantly differ among FFs, POs, and OWs (p > 0.6). The left ventricular mass (LV Mass) was notably higher in POs than it was in FFs (p = 0.039) and OWs (p = 0.033). Strain parameter differences were notably improved in two- (p = 0.006) and four-chamber (p = 0.018) views for FFs compared to POs. Concentric remodeling was the predominant change observed in all three occupational groups. Significant differences in the presence of various forms of hypertrophy were observed in FFs, POs, and OWs (exact Fisher test p-values: FFs vs. OWs = 0.021, POs vs. OWs = 0.002). OWs demonstrated notably higher rates of concentric remodeling than FFs did (71.77% vs. 47.9%). This study underscores disparities in both functional and structural parameters in diverse occupational groups. Larger prospective studies are warranted to investigate and delineate differences in structural and functional cardiac parameters across occupational groups, and to discern their associated effects and risks on the cardiovascular health of these distinct professional cohorts.

Comparative analysis of ventricular stiffness across species.

Investigating ventricular diastolic properties is crucial for understanding the physiological cardiac functions in organisms and unraveling the pathological mechanisms of cardiovascular disorders. Ventricular stiffness, a fundamental parameter that defines ventricular diastolic functions in chordates, is typically analyzed using the end-diastolic pressure-volume relationship (EDPVR). However, comparing ventricular stiffness accurately across chambers of varying maximum volume capacities has been a long-standing challenge. As one of the solutions to this problem, we propose calculating a relative ventricular stiffness index by applying an exponential approximation formula to the EDPVR plot data of the relationship between ventricular pressure and values of normalized ventricular volume by the ventricular weight. This article reviews the potential, utility, and limitations of using normalized EDPVR analysis in recent studies. Herein, we measured and ranked ventricular stiffness in differently sized and shaped chambers using ex vivo ventricular pressure-volume analysis data from four animals: Wistar rats, red-eared slider turtles, masu salmon, and cherry salmon. Furthermore, we have discussed the mechanical effects of intracellular and extracellular viscoelastic components, Titin (Connectin) filaments, collagens, physiological sarcomere length, and other factors that govern ventricular stiffness. Our review provides insights into the comparison of ventricular stiffness in different-sized ventricles between heterologous and homologous species, including non-model organisms.

Stronger positive correlation of the left ventricular mass index and extracellular volume fraction with diastolic function in diabetic patients without myocardial infarction.

BACKGROUND: The structural and functional characteristics of the heart in patients with diabetes mellitus (DM) and without myocardial infarction (MI) are not fully understood. METHODS: We retrospectively analysed the data of patients with left ventricular ejection fraction (LVEF) ≥ 40% who underwent contrast-enhanced cardiac magnetic resonance imaging (CMR), which was also used to exclude MI, at two hospitals. Volumetric data and extracellular volume fraction (ECVf) of the myocardium evaluated using CMR were compared between patients with and without DM, and their association with diastolic function was evaluated. RESULTS: Among 322 analysed patients, 53 had DM. CMR revealed that the left ventricular mass index (LVMi) and ECVf were increased while LVEF was decreased in patients with DM after adjusting for patient characteristics (all P < 0.05). A stronger positive correlation was observed between LVMi and the early diastolic transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') in patients with DM than in those without DM (correlation coefficient [R] = 0.46, p = 0.001; R = 0.15, p = 0.021, respectively; p for interaction = 0.011). ECVf correlated with E/e' only in patients with DM (R = 0.61, p = 0.004). CONCLUSIONS: Patients with DM have increased LVMi and ECVf. Importantly, there was a difference between patients with and without DM in the relationship between these structural changes and E/e', with a stronger relationship in patients with DM. Furthermore, DM is associated with mildly reduced LVEF even in the absence of MI.

Systolic and diastolic blood pressure time in target range and cardiovascular outcomes in patients with hypertension and pre-frailty or frailty status.

In patients with hypertension and pre-frailty or frailty, the influence of systolic (SBP) and diastolic blood pressure (DBP) time in target range (TTR) on clinical outcomes is unclear. Thus, we conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). Classifying 4208 participants into frail and non-frail groups using a frailty index, the study calculated blood pressure time in target range (BP-TTR) for the first three months using the Rosendaal method. The primary endpoint included a composite of nonfatal myocardial infarction (MI), acute coronary syndromes, stroke, acute decompensated heart failure (ADHF), and cardiovascular death. Relationships between BP-TTR and outcomes were analyzed using Kaplan-Meier curves, Cox models, and restricted cubic spline curves, with subgroup analysis for further insights. In a median follow-up of 3.17 years, primary outcomes occurred in 6.7% of participants. Kaplan-Meier analysis showed that a lower systolic blood pressure time in target range (SBP-TTR) (0%-25%) correlated with an increased cumulative incidence of the primary outcome (p < .001), nonfatal MI (P = .021), stroke (P = .004), and cardiovascular death (P = .002). A higher SBP-TTR (75%-<100%) was linked to a reduced risk of these outcomes. The restricted cubic spline (RCS) curve revealed a linear association between SBP-TTR and the primary outcome (non-linear P = .704). Similar patterns were observed for diastolic blood pressure time in target range (DBP-TTR). Subgroup analysis showed that the protective effect of higher SBP-TTR was less pronounced at low DBP-TTR levels (P for interaction = .023). In conclusion, this study highlights the importance of maintaining BP within the target range to mitigate cardiovascular risks in this population.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Evaluation of cardiac electrophysiological features in patients with premature adrenarche.

OBJECTIVES: This study aimed to analyze the cardiac effects of hyperandrogenism in premature adrenarche (PA) and evaluate the risk of arrhythmia development. METHODS: Fifty patients with PA and 50 healthy children from a pediatric endocrinology outpatient clinic were included in the study. The patients underwent echocardiography and electrocardiographic evaluations. Conventional echocardiography, tissue Doppler echocardiography, repolarization time, and repolarization dispersion time were evaluated. RESULTS: The median age in the PA and control groups was 7.91 years (5.83-9.25), 8.08 years (5.75-9.33), respectively. Thirty percent of patients in the PA group were male. While mitral early diastolic velocity deceleration time (DT), isovolumetric relaxation time (IRT), and E/e' ratio were significantly higher in the PA group than in the control group, mitral lateral annulus tissue Doppler early diastolic velocity was significantly lower (p=0.0001, 0.0001, 0.003, 0.0001). While P wave dispersion (PWD), Tpe, and QT-dispersion (QT-d) values were significantly higher in the PA group than in the control group, the P minimum value was significantly lower in the PA group (p=0.0001, 0.02, 0.004, and 0.0001, respectively). CONCLUSIONS: Early subclinical diastolic dysfunction was observed in the PA group. There was an increased risk of atrial arrhythmia with PWD and an increased risk of ventricular arrhythmia with increased Tpe and QT-d. There was a correlation between testosterone levels and diastolic function parameters. The increased risk of atrial arrhythmia is closely related to diastolic function.

15 weeks of soccer training increases left ventricular mass and improves indices of left ventricular diastolic function in previously sedentary, mildly hypertensive, middle-aged women.

PURPOSE: To investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women. METHODS: Hypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.6 kg; body fat: 43.3 ± 5.2%) were randomized to soccer training (SOC, n = 21) or control (CON, n = 20). SOC performed three weekly training sessions for 15 weeks, whereas CON had no training or lifestyle changes during the same period. Cardiac structure and function were assessed by echocardiography pre-intervention and post-intervention. RESULTS: Soccer training increased (P = 0.001) left ventricular mass index by 10% [95% CI 4; 15], while no changes occurred in CON (time × group interaction, P = 0.005). In addition, only SOC demonstrated a within-group increase (P = 0.01) of 8% [95% CI 2; 14] in left ventricular septum diameter. For markers of right ventricular remodelling, a within-group increase (P = 0.02) occurred for tricuspid annulus plane systolic excursion of 8% [95% CI 1; 14] in SOC only. Left atrial diameter index increased (P < 0.001) by 6% [95% CI 3; 10] after SOC, while it was unaffected in CON (time × group interaction, P = 0.02). For makers of diastolic function, SOC demonstrated a within-group increase (P = 0.02) in the average early diastolic mitral annulus velocity of 10% [95% CI 2; 19]. In addition, a reduction (P < 0.001) in mitral valve A velocity of - 19% [95% CI - 29; - 10] was observed following soccer training, which manifested in increased (P < 0.001) mitral valve E/A ratio of 34% [95% CI 16; 53] in SOC. No within-group changes were apparent in CON. CONCLUSION: In sedentary, mildly hypertensive, middle-aged women, 15 weeks of soccer training increases left ventricular mass and left atrial diameter and improves indices of left ventricular diastolic function.

The cardiomyocyte origins of diastolic dysfunction: cellular components of myocardial "stiffness".

The impaired ability of the heart to relax and stretch to accommodate venous return is generally understood to represent a state of "diastolic dysfunction" and often described using the all-purpose noun "stiffness." Despite the now common qualitative usage of this term in fields of cardiac patho/physiology, the specific quantitative concept of stiffness as a molecular and biophysical entity with real practical interpretation in healthy and diseased hearts is sometimes obscure. The focus of this review is to characterize the concept of cardiomyocyte stiffness and to develop interpretation of "stiffness" attributes at the cellular and molecular levels. Here, we consider "stiffness"-related terminology interpretation and make links between cardiomyocyte stiffness and aspects of functional and structural cardiac performance. We discuss cross bridge-derived stiffness sources, considering the contributions of diastolic myofilament activation and impaired relaxation. This includes commentary relating to the role of cardiomyocyte Ca2+ flux and Ca2+ levels in diastole, the troponin-tropomyosin complex role as a Ca2+ effector in diastole, the myosin ADP dissociation rate as a modulator of cross bridge attachment and regulation of cross-bridge attachment by myosin binding protein C. We also discuss non-cross bridge-derived stiffness sources, including the titin sarcomeric spring protein, microtubule and intermediate filaments, and cytoskeletal extracellular matrix interactions. As the prevalence of conditions involving diastolic heart failure has escalated, a more sophisticated understanding of the molecular, cellular, and tissue determinants of cardiomyocyte stiffness offers potential to develop imaging and molecular intervention tools.

Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm2), left ventricular area end diastole (mm2), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.

Sex-Specific Limitation of Cardiac Capacity During the Adult Life Span: Return to Fundamental Structure and Function.

Physiology underlying reduced cardiac pumping capacity in women compared with men and its interaction with aging remains unresolved. Herein, the pressure gradient (PG) driving venous return was manipulated to evidence whether cardiac structure and/or function explain sex differences in cardiac capacity. Healthy women/men matched by age and physical activity were included within young (n = 40, age = 25 ±â€…4 years) and older (n = 55, age = 60 ±â€…8 years) groups. Cardiac volumes/output (Q) were assessed up-to-peak exercise under 2 hemodynamic conditions ("low"/"high" PG between lower/upper body). Main outcomes included sex differences in delta ("high" - "low" PG) left ventricular (LV) end-diastolic volume (∆LVEDV), stroke volume (∆SV), and Q (∆Q). In young individuals, "high"-PG increased exercise LVEDV and SV in men (p ≤ .002), but not in women (p ≥ .562), relative to "low"-PG (control condition). Accordingly, peak ∆LVEDV, ∆SV, and ∆Q were enhanced in young men versus young women (p ≤ .019). Notwithstanding, right/left atrial volumes during exercise were similarly increased by "high"-PG in both young sexes (p ≤ .007). "High"-PG exclusively prolonged moderate exercise LV filling time in young men (p ≤ .036). In older individuals, "high"-PG did not modify exercise cardiac volumes and reduced LV diastolic function (p ≤ .049). In conclusion, the female young heart is unrestrained by venous return or structural factors external to the myocardium. As determined during moderate exercise, impaired LV filling time lengthening limits female-specific cardiac capacity. With older age, cardiac chambers are not distended and LV relaxation is impaired with increased PG in both sexes. During early but not late adulthood, a functional LV limitation may explain sex differences in cardiac capacity.

Increased Blood Pressure Variability Over a 16-Year Period Is Associated With Left Ventricular Diastolic Dysfunction in a Population-Based Cohort.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is often associated with elevated blood pressure (BP). It is prevalent among hypertensive patients. Additionally, increased BP variability has been linked to LVDD. However, the precise connection between LVDD and BP variability within the general population remains unclear. Thus, this study aimed to evaluate this association in a general population. METHODS: A total of 2,578 participants(1,311 females) with a mean age of 47.8 ±â€…6.7 years who had echocardiographic data from the Korean Genome and Epidemiology study with 16 years of follow-up were analyzed. LVDD was identified through the last echocardiography during the follow-up period. BP variability was assessed using mean, standard deviation (SD), and coefficient of variance (CV). RESULTS: LVDD was detected in 249 individuals. The cohort was divided into an LVDD group and a normal LV diastolic function group. The LVDD group had a higher percentage of females, more advanced age, higher body mass index (BMI), higher BP and BUN levels, lower heart rate, lower hemoglobin, and lower serum creatinine than the normal LV diastolic function group. Remarkably, LVDD was associated with higher BP variability. In the multivariate analysis, LVDD was associated with increased age, female sex, increased BMI, hypertension, and increased BUN. Elevated mean systolic and diastolic BPs, SD of systolic BP, mean pulse pressure (PP), SD of PP, and CV of PP were significantly linked to LVDD even after adjusting for other significant variables in the multivariate analysis. CONCLUSIONS: LVDD was identified in 249 (9.7%) participants. Increased long-term BP variability was significantly associated with LVDD in this population-based cohort.

Impact of Hypertension on Left Ventricular Geometry and Diastolic Function in Africa: Results from the Population-Based TAnve Health (TAHES) Cohort Study.

High blood pressure leads to morphologic changes and functional alterations of the myocardial structure. Transthoracic echocardiography is of great clinical interest to evaluate these alterations, using reference values proposed by the American Society of Echocardiography/European Association of Cardiovascular Imaging, largely based on studies in Caucasian Whites. We aimed to assess the impact of hypertension on echocardiographic parameters in a sub-Saharan African community, using ethnic-specific reference values. This study is part of the TAnve HEalth Study, a population-based prospective cohort study initiated in 2015 in the district of Tanve, Republic of Benin. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or currently taking antihypertensive medications. All participants had a transthoracic echocardiography. The patterns of diastolic dysfunction and left ventricular (LV) geometry were defined from 486 subjects in the cohort, free from cardiovascular disease, diabetes, and hypertension. Of all participants, 318 (65% women, median age 48 years) had hypertension. Systolic blood pressure correlated significantly (p <0.0001) with LV mass (r = 0.28), wall thickness (r = 0.25), isovolumic relaxation time (r = 0.27), E/A ratio (r = -0.35), lateral e' velocity (r= -0.41), and E/E' ratio (r = 0.39). Ventricular geometry was normal in only 22% of participants with hypertension when using the American Society of Echocardiography/European Association of Cardiovascular Imaging reference values, versus 69% with ethnic-specific reference ranges. The severity of hypertension was associated with ventricular geometry abnormalities. The prevalence of diastolic dysfunction was 14.5% (confidence interval 10.6% to 18.4%), including relaxation impairment (9%) and pseudonormal pattern (6%). Thus, correct assessment of the repercussions of hypertension on LV geometry in Black Africans requires ethnic-specific reference values.

Pulse Pressure is Sex-Specifically Associated with the Ratio of Diastolic and Systolic Arterial Pressure in Healthy Children, and Differently During Night Versus Daytime Recordings.

Noninvasive blood pressure recordings typically focus on systolic blood pressure (SBP) and diastolic pressure (DBP). Derived metrics are often analyzed, e.g. pulse pressure (PP), defined as SBP minus DBP. As the metric PP is not unique, we introduced the PP companion (PPC), calculated using the Pythagorean theorem. PPC is associated with mean arterial pressure (MAP). Another mathematical construct frequently used in hemodynamic studies refers to the ratio of DBP and SBP, denoted as Prat. PP and Prat share the same companion (C). The association between PratC and MAP, as well as the connection between PP and Prat has not been studied in healthy children. We analyzed a large set of daytime (DT) and nighttime (NT) data (N=949, age 5 to 16 years, including 485 girls), published in the literature. Average PP increases with age (in 0.5 year increments), while Prat decreases. Prat vs PP yields R2>0.985 for both DT and NT data, when stratified for boys and girls. PPC is significantly lower (P<0.0001) during the night for both sexes. We conclude that Prat carries no substantial incremental value beyond PP, in contrast to PPC which points to DT/NT, age-dependent and sex-specific differences in these children.Clinical Relevance- Various derived metrics based on blood pressure have been introduced in hemodynamic studies, but not all of them are fully independent. The diastolic to systolic pressure ratio in healthy children is inversely associated with pulse pressure, showing partial sex-specific overlap, but substantial daytime versus night differences.