Conduit Arteries Research Articles

Pulmonary edema in a young male with severe uncontrolled cardiovascular risk factors and pan-vascular atherosclerosis: a case report.

Cardiovascular risk factors are the cause of atherosclerotic disease, which can involve all the elastic and muscolo-elastic arteries. The etiopathogenesis of atherosclerosis is multifactorial since genetics, lifestyle, and comorbidities can be simultaneously involved. Clinical manifestations can be heterogeneous and include myocardial infarction, stroke, aortic aneurysms, renal artery stenosis, renal insufficiency, peripheral artery disease, etc. Currently, 70% of clinical events cannot be prevented with available drug therapy, statins included, and at least 10% of coronary events occur in apparently healthy individuals in the absence of major traditional risk factors. The case of a young male with a history of coronary artery disease and multiple atherosclerotic risk factors not properly treated who was admitted to the emergency department for pulmonary edema and high blood pressure is presented. During the diagnostic workup, a dramatic atherosclerotic involvement of all arterial trees emerged. Moreover, the patient presented with thrombosis of the right subclavian artery, which was treated with a heparin infusion and later complicated by cerebral hemorrhage with residual hemiplegia.

Longitudinal changes in the carotid arteries of head and neck cancer patients following radiation therapy: Results from a prospective serial imaging biomarker characterization study

IntroductionWe prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer. MethodsBilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated. ResultsThirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs −0.003 mm; P = 0.014), which increased at 3 and 4 years (0.128 mm vs 0.013 mm, P = 0.016, and 0.177 mm vs 0.023 mm, P = 0.0002, respectively). A significant transient change was noted in global circumferential strain between the irradiated and unirradiated arteries at 6 months (median difference, −0.89, P = 0.023), which did not persist. No significant differences were detected in the other measures of elasticity, stiffness, and distensibility. ConclusionsFunctional and morphologic changes of the carotid arteries detected by carotid ultrasound, such as changes in global circumferential strain at 6 months and carotid IMT at 18 months, may be useful for the early detection of radiation-induced carotid artery injury, can guide future research aiming to mitigate carotid artery stenosis, and should be considered for clinical surveillance survivorship recommendations after head and neck RT.

Investigation of Rupture Risk of Thoracic Aortic Aneurysms via Fluid–Structure Interaction and Artificial Intelligence Method

Patient-specific studies on vascular flows have significantly increased for hemodynamics due to the need for different observation techniques in clinical practice. In this study, we investigate aortic aneurysms in terms of deformation, stress, and rupture risk. The effect of Ascending Aortic Diameter (AAD) was investigated in different aortic arches (19.81 mm, 42.94 mm, and 48.01 mm) via Computational Fluid Dynamics (CFD), Two-way coupling Fluid–Structure Interactions (FSI) and deep learning. The non-newtonian Carreau viscosity model was utilized with patient-specific velocity waveform. Deformations, Wall Shear Stresses (WSSs), von Mises stress, and rupture risk were presented by safety factors. Results show that the WSS distribution is distinctly higher in rigid cases than the elastic cases. Although WSS values rise with the increase in AAD, aneurysm regions indicate low WSS values in both rigid and elastic artery solutions. For the given AADs, the deformations are 2.75 mm, 6. 82 mm, and 8.48 mm and Equivalent von Mises stresses are 0.16 MPa, 0.46 MPa, and 0.53 MPa. When the rupture risk was evaluated for the arteries, the results showed that the aneurysm with AAD of 48.01 mm poses a risk up to three times more than AAD of 19.81 mm. In addition, an Artificial neural network (ANN) method was developed to predict the rupture risk with a 98.6% accurate prediction by numerical data. As a result, FSI could indicate more accurately the level of rupture risk than the rigid artery assumptions to guide the clinical assessments and deep learning methods could decrease the computational costs according to CFD and FSI.

The effect of short-term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study.

Patients with chronic kidney disease (CKD) are more susceptible to endothelial dysfunction and cardiovascular disease (CV). Remote ischemic preconditioning (rIPC) has been proven efficient in improving endothelial function and lowering the risk of CV. However, the safety and effect of rIPC on endothelial function in patients with CKD have not been effectively assessed. 45 patients with CKD (average estimated glomerular filtration rate: 48.4 mL/min/1.73 m2) were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 200 mmHg, interspaced by 5-min reperfusion) or control (4 × 5 min 60 mmHg, interspaced by 5-min reperfusion). Vascular endothelial function was assessed by natural log-transformed reactive hyperemia index (LnRHI) before and after a 7-day intervention. Arterial elasticity was assessed by augmentation index (AI). The results showed that LnRHI could be improved by rIPC treatment (Pre = 0.57 ± 0.04 vs. Post = 0.67 ± 0.04, p = .001) with no changes relative to control (Pre = 0.68 ± 0.06 vs. Post = 0.64 ± 0.05, p = .470). Compared with the control group, the improvement of LnRHI was greater after rIPC treatment (rIPC vs. Control: 0.10 ± 0.03 vs. -0.04 ± 0.06, between-group mean difference, -0.15 [95% CI, -0.27 to -0.02], p = .027), while there was no significant difference in the change of AI@75 bpm (p = .312) between the two groups. RIPC is safe and well tolerated in patients with CKD. This pilot study suggests that rIPC seems to have the potential therapeutic effect to improve endothelial function. Of note, further larger trials are still warranted to confirm the efficacy of rIPC in improving endothelial function in CKD patients.

Subclinical atherosclerosis in young adults predicting cardiovascular disease: The Cardiovascular Risk in Young Finns Study

Background and aimsAtherosclerosis is accompanied by pre-clinical vascular changes that can be detected using ultrasound imaging. We examined the value of such pre-clinical features in identifying young adults who are at risk of developing atherosclerotic cardiovascular disease (ASCVD). MethodsA total of 2641 individuals free of ASCVD were examined at the mean age of 32 years (range 24–45 years) for carotid artery intima-media thickness (IMT) and carotid plaques, carotid artery elasticity, and brachial artery flow-mediated endothelium-dependent vasodilation (FMD). The average follow-up time to event/censoring was 16 years (range 1–17 years). ResultsSixty-seven individuals developed ASCVD (incidence 2.5%). The lowest incidence (1.1%) was observed among those who were estimated of having low risk according to the SCORE2 risk algorithm (<2.5% 10-year risk) and who did not have plaque or high IMT (upper decile). The highest incidence (11.0%) was among those who were estimated of having a high risk (≥2.5% 10-year risk) and had positive ultrasound scan for carotid plaque and/or high IMT (upper decile). Carotid plaque and high IMT remained independently associated with higher risk in multivariate models. The distributions of carotid elasticity indices and brachial FMD did not differ between cases and non-cases. ConclusionsScreening for carotid plaque and high IMT in young adults may help identify individuals at high risk for future ASCVD.

Реєстр PULSE-COR: взаємозв’язок між еластичністю лівого шлуночка та жорсткістю артерій у пацієнтів з есенціальною артеріальною гіпертензією

For a long time, the problem of the formation of diastolic dysfunction (DD) of the left ventricle (LV) in patients with arterial hypertension (AH) remained insufficiently studied. It was demonstrated that the formation of LV DD is largely related to the increase in stiffness of this heart chamber. We decided to evaluate the extent to which increased LV stiffness, determined noninvasively by echocardiography, is associated with LV diastolic dysfunction and determine the relationship of this method with arterial stiffness indicators for which validated methods have been developed.Materials and methods. A one-center registry called PULSE-COR was established in 2011 and is still in operation. There were 779 AH participants in our sample. A distinct cohort of patients (n=283) with essential AH and no substantial comorbidities were found from the final analysis, which comprised 320 patients who had undergone all requisite diagnostic procedures. Our tool of choice for measuring carotid-femoral pulse wave velocity (cfPWV) was the SphygmoCor device (AtCor, Australia). We also used the VaSera 1500 device (Fukuda Denshi, Japan) to measure cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI). Vascular ultrasound and intima-media thickness measurement (IMT) were included in the ultrasound diagnosis. The ASE 2016 recommendations were followed for the evaluation of diastolic LV function, and the standardized ASE protocol was followed for echocardiography. A standardized formula was used to assess the ventriculo-arterial coupling (VAC) which also included LV end-systolic elastance (Ees) and arterial elastance (Ea) evaluation. We conducted Spearman correlation analysis to identify relationships.Results and discussion. Our cohort were patients with AH, 51 % males; the mean age was 53.6±2.0 years. Mean office blood pressure (BP) was 159.8±4.5 mm Hg for systolic (SBP), 97.9±2.6 mm Hg for diastolic (DBP), 62.0±3.5 mm Hg for pulse blood (PBP) BP, and 76.6±2.2 bits per minute was the mean heart rate (HR). Both the left and right CAVI (R=0.698; p=0.012 and R=0.683; p=0.014) showed a strong correlation with VAC. Both E/A and E/e showed a substantial correlation with ABI (R=0.716; p=0.006 and R=0.764; p=0.002, respectively). cfPWV was linked with nearly the same parameters (R=0.248; p=0.001 for correlation with IMT, R=0.382; p=0.01 for correlation with low-density lipoproteins). Ea was substantially associated with IMT (R=0.491; p=0.24), total cholesterol (R=0.499; p=0.07), and low-density lipoproteins (R=0.687; p=0.001). Ees was substantially correlated with end diastolic volume (R=0.644; p=0.001), blood lymphocytes (R=–0.678; p=0.001), E/A (R=0.159; p=0.007), and E/e’ (R=–0.130; p=0.029).Conclusions. We have found a substantial correlation between validated arterial stiffness measurements and non-invasive LV stiffness evaluation parameters (VAC). VAC also was associated with LV diastolic function parameters

Effect of age and gender on ventricular-arterial coupling estimated using a non-invasive technique

BackgroundLeft ventricular-arterial coupling is assessed as the ratio of left ventricular end-systolic elastance (Ees) to arterial elastance (Ea). Previous studies have introduced non-invasive estimations of Ees/Ea. It requires only four variables, namely pre-ejection period, ejection time, end-systolic pressure and diastolic pressure. The aims of the present study were to clarify the reference values of Ees/Ea estimated using the noninvasive technique, and to investigate the effects of age and gender on Ees/Ea in healthy subjects.MethodsThis retrospective study utilized data from healthy, 30-79-year-old subjects. We recorded electrocardiogram, phonocardiogram, and brachial arterial pulse waves simultaneously using the vascular screening system, and used the observed variables to calculate Ees/Ea. We separated subjects into five groups according to their age and compared Ees/Ea among the different age groups.ResultsThe study included 2114 males and 2292 females. Ees/Ea ranged from 1.87 to 2.04 in males, and 1.98 to 2.32 in females. We observed no age-related differences in Ees/Ea in males (p = 0.10), and significant differences in females (p < 0.001). Ees/Ea in males was not different compared to those in females in 60-69-year-old group (p = 0.92). Whereas Ees/Ea was higher in females compared to those in males in the other age groups. The differences between medians of Ees/Ea in males and those in females were 0.45 (p < 0.001), 0.24 (p < 0.001), 0.13 (p = 0.01), and 0.13 (p = 0.03) in 30–39, 40–49, 50–59, and 70-79-year-old age groups, respectively.ConclusionsWe clarified the reference values of Ees/Ea in healthy subjects. The effect of age on Ees/Ea is different in males and females, although Ees/Ea is maintained within a relatively narrow range in all subjects.

Low Mean Perfusion Pressure Indexed to Body Surface Area is a Powerful Predictor of Poor Outcomes After Heart Transplantation in Patients With High Pre-Transplant Venous Pressure: A Clinical Study With Physiological Insights From Mathematical Modelling of Biventricular Heart Failure

The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (Ea) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, Ea calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. High RAP was a significant risk factor for short-term and medium-term survival if Ea was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (p∼0.005). When Ea was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (p∼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (r∼-0.3580, p<0.0001) as well as creatinine (r∼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, p∼0.001) and medium-term survival. The impact of high RAP and low Ea on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low Ea vs 75% for RAP<15 mmHg (p∼0.0033). The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation.

Dynamic arterial elastance as a predictor of arterial pressure response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome-a systematic review and meta-analysis.

During the de-escalation phase of circulatory shock, norepinephrine weaning may induce diverse arterial pressure responses in patients with different vasomotor tones. Dynamic arterial elastance (Eadyn) has been extensively studied to predict the arterial pressure response to interventions. We conducted this meta-analysis to systematically assess the predictive performance of Eadyn for the mean arterial pressure (MAP) response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. A systematic literature search was conducted on May 29, 2023 (updated on January 21, 2024), to identify relevant studies from electronic databases. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy because of the varied thresholds reported. Additionally, we observed the distribution of the cutoff values of Eadyn, while computing the optimal value and its corresponding 95% confidential interval (CI). A total of 5 prospective studies met eligibility, comprising 183 participants, of whom 67 (37%) were MAP responders. Eadyn possessed an excellent ability to predict the MAP response to norepinephrine weaning in patients with vasoplegic syndrome, with an AUHSROC of 0.93 (95% CI: 0.91-0.95), a pooled sensitivity of 0.94 (95% CI: 0.85-0.98), a pooled specificity of 0.73 (95% CI: 0.65-0.81), and a pooled diagnostic odds ratio of 32.4 (95% CI: 11.7-89.9). The cutoff values of Eadyn presented a nearly conically symmetrical distribution; the mean and median cutoff values were 0.89 (95% CI: 0.80-0.98) and 0.90 (95% CI: not estimable), respectively. This meta-analysis with limited evidences demonstrates that Eadyn may be a reliable predictor of the MAP response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. PROSPERO CRD42023430362.

Renal denervation improves cardiac function independently of afterload and restores myocardial norepinephrine levels in a rodent heart failure model

Renal nerves play a critical role in cardiorenal interactions. Renal denervation (RDN) improved survival in some experimental heart failure (HF) models. It is not known whether these favorable effects are indirect, explainable by a decrease in vascular afterload, or diminished neurohumoral response in the kidneys, or whether RDN procedure per se has direct myocardial effects in the failing heart. To elucidate mechanisms how RDN affects failing heart, we studied load-independent indexes of ventricular function, gene markers of myocardial remodeling, and cardiac sympathetic signaling in HF, induced by chronic volume overload (aorto-caval fistula, ACF) of Ren2 transgenic rats. Volume overload by ACF led to left ventricular (LV) hypertrophy and dysfunction, myocardial remodeling (upregulated Nppa, MYH 7/6 genes), increased renal and circulating norepinephrine (NE), reduced myocardial NE content, increased monoaminoxidase A (MAO-A), ROS production and decreased tyrosine hydroxylase (+) nerve staining. RDN in HF animals decreased congestion in the lungs and the liver, improved load-independent cardiac function (Ees, PRSW, Ees/Ea ratio), without affecting arterial elastance or LV pressure, reduced adverse myocardial remodeling (Myh 7/6, collagen I/III ratio), decreased myocardial MAO-A and inhibited renal neprilysin activity. RDN increased myocardial expression of acetylcholinesterase (Ache) and muscarinic receptors (Chrm2), decreased circulating and renal NE, but increased myocardial NE content, restoring so autonomic control of the heart. These changes likely explain improvements in survival after RDN in this model. The results suggest that RDN has remote, load-independent and favorable intrinsic myocardial effects in the failing heart. RDN therefore could be a useful therapeutic strategy in HF.

Evaluation of ventricular-vascular coupling with critical care metrics: An in silico approach.

Mean arterial pressure and cardiac output provide insufficient guidance for the management of intraoperative hypotension (IOH). In silico models offer additional insights into acute changes in hemodynamic parameters that may be encountered during IOH. A computational model (CM) generated parameters quantifying ventricular-vascular coupling, and pressure-volume construct across levels of aortic compliance (CA ). We studied how a loss from normal-to-stiff CA impacts critical care metrics of hemodynamics during vascular occlusion. Pulse pressure (PP), end-systolic pressure (Pes ), arterial compliance (Art-ca), arterial elastance (Art-ea), and dynamic arterial elastance (Eadyn), along mechanical efficiency (ME) were measured at five levels of CA . A loss in CA impacted all variables. During steady-state conditions, PP, Pes , and stroke work increased significantly as CA decreased. Art-ca decreased and Art-ea increased similarly; Eadyn increased and ME decreased. During a decrease in preload across all CA levels, arterial dynamics measures remained linear. The CM demonstrated that a loss in CA impacts measures of arterial dynamics during steady-state and transient conditions and the model demonstrates that critical care metrics are sensitive to changes in CA . While Art-ca and Art-ea were sensitive to changes in preload, Eadyn did not change.

Distinctive left ventricular-arterial and right ventricular-pulmonary arterial coupling observed in patients with heart failure and a higher left ventricular ejection fraction range.

Higher left ventricular (LV) ejection fraction (EF) is related to unfavourable prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The cause of this finding needs to be haemodynamically explained. Thus, we investigated this crucial issue from the perspective of LV-arterial (A) and right ventricular (RV)-pulmonary arterial (PA) coupling. Study patients were derived from our prospective cohort study of patients hospitalized due to acute decompensated HF and LVEF > 40%. We divided the 255 patients into three groups: HF with mildly reduced EF (HFmrEF), HFpEF with 50% ≤ LVEF < 60%, and HFpEF with LVEF ≥ 60%. We compared LV end-systolic elastance (Ees), effective arterial elastance (Ea), and Ees/Ea as a representative of LV-A coupling among groups and compared the ratio of tricuspid annular plane excursion to peak pulmonary arterial systolic pressure (TAPSE/PASP) as a representative of RV-PA coupling. All-cause death and readmission due to HF-free survival was worse in the group with a higher LVEF range. Ees/Ea was greater in HFpEF patients with LVEF ≥ 60% (2.12 ± 0.57) than in those with 50% ≤ LVEF < 60% (1.20 ± 0.14) and those with HFmrEF (0.82 ± 0.09) (P < 0.001). PASP was increased in the groups with higher LVEF; however, TAPSE/PASP did not differ among groups (n = 168, P = 0.17). In a multivariate Cox proportional hazard model, TAPSE/PASP but not PASP was significantly related to event-free survival independent of LVEF. HFpEF patients with higher LVEF have unfavourable prognosis and distinctive LV-A coupling: Ees/Ea is elevated up to 2.0 or more. Impaired RV-PA coupling also worsens prognosis in such patients. URL: https://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000017725.

Histamine H2-receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II–hypertensive mice

Aldosterone through the mineralocorticoid receptor MR has detrimental effects on cardiovascular disease. It reduces the bioavailability of nitric oxide and impairs endothelium-dependent vasodilatation. In resistance arteries, aldosterone impairs the sensitivity of vascular smooth muscle cells to nitric oxide by promoting the local secretion of histamine which activates H2 receptors. The present experiments tested in vivo and ex vivo the hypothesis that systemic H2-receptor antagonism reduces arterial blood pressure and improves vasodilatation in angiotensin II–induced chronic hypertension. Hypertension was induced by intravenous infusion of angiotensin II (60 ng kg−1 min−1) in conscious, unrestrained mice infused concomitantly with the H2-receptor antagonist ranitidine (27.8 µg kg−1 min−1) or vehicle for 24 days. Heart rate and arterial blood pressure were recorded by indwelling arterial catheter. Resistance (mesenteric) and conductance (aortae) arteries were harvested for perfusion myography and isometric tension recordings by wire myography, respectively. Plasma was analyzed for aldosterone concentration. ANGII infusion resulted in elevated arterial blood pressure and while in vivo treatment with ranitidine reduced plasma aldosterone concentration, it did not reduce blood pressure. Ranitidine improved ex vivo endothelial function (acetylcholine 10−9 to 10−6 mol L−1) in mesenteric resistance arteries. This was abolished by ex vivo treatment with aldosterone (10−9 mol L−1, 1 h). In aortic segments, in vivo ranitidine treatment impaired relaxation. Activation of histamine H2 receptors promotes aldosterone secretion, does not affect arterial blood pressure, and protects endothelial function in conduit arteries but promotes endothelial dysfunction in resistance arteries during angiotensin II–mediated hypertension. Aldosterone contributes little to angiotensin II–induced hypertension in mice.

The knowledge of movement experts about stretching effects: Does the science reach practice?

Stretching is performed with numerous purposes in multiple settings such as prevention, rehabilitation, fitness training and sports. Its patterns of use substantially depend on the education and beliefs of health care and exercise professionals as they represent the multiplicators recommending and prescribing interventions to clients, patients and athletes. This study investigated movement experts' knowledge about the scientific evidence on stretching effects. Survey study. A total of 117 exercise and health professionals (physiotherapists, sports scientists, coaches) attending a training convention in Austria (male: n = 44, female: n = 73, 36±11 years) completed a digital survey. With its 22 items, the questionnaire addressed the movement experts' awareness of the evidence on stretching effects regarding a variety of related topics selected based on the findings of topical systematic reviews. The majority of the individuals (57-88%) assumed positive effects of stretching on recovery, prevention of muscle injury, range of motion, muscular imbalance and artery elasticity. No or adverse effects were mostly claimed on bone injury prevention, maximal/explosive strength, and delayed-onset muscle soreness. In only 10 of 22 items, participants' classifications were in accord with the scientific evidence. The awareness of research findings on stretching effects among exercise and health professionals is alarmingly low. Future studies may hence be geared to improve implementation and science communication.

Intermediate versus morning chronotype has lower vascular insulin sensitivity in adults with obesity.

Chronotype reflects a circadian rhythmicity that regulates endothelial function. While the morning chronotype (MORN) usually has low cardiovascular disease risk, no study has examined insulin action on endothelial function between chronotypes. We hypothesized intermediate chronotypes (INT) would have lower vascular insulin sensitivity than morning chronotype (MORN). Adults with obesity were classified per Morningness-Eveningness Questionnaire (MEQ) as either MORN (n = 27, 22 female, MEQ = 63.7 ± 4.7, 53.8 ± 6.7 years, 35.3 ± 4.9 kg/m2) or INT (n = 29, 23 female, MEQ = 48.8 ± 6.7, 56.6 ± 9.0 years, 35.7 ± 6.1 kg/m2). A 120 min euglycaemic-hyperinsulinaemic clamp (40 mU/m2/min, 90 mg/dl) was conducted to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD; conduit artery), post-ischaemic flow velocity (resistance arteriole), as well as microvascular insulin sensitivity via contrast-enhanced ultrasound [e.g. microvascular blood volume (perfusion)]. Fasting plasma arginine and citrulline, as well as fasting and clamp-derived plasma endothelin-1 and nitrate/nitrite, were assessed as surrogates of vasoconstriction and nitric oxide-mediated vasodilation. Aerobic fitness (VO2max) and body composition (dual-energy X-ray absorptiometry) were also collected. MORN had a higher VO2max compared with INT (p < .01), although there was no difference in fat mass. While fasting FMD was similar between groups, insulin lowered FMD corrected to shear stress and microvascular blood volume in INT compared with MORN after co-varying for VO2max (both p ≤ .02). INT also had a lower fasting nitrate (p = .03) and arginine (p = .07). Higher MEQ correlated with elevated FMD (r = 0.33, p = .03) and lower post-ischaemic flow velocity (r = -0.33, p = .03) as well as shear rate (r = -0.36, p = .02) at 120 min. When measured during the morning, INT had a lower vascular insulin sensitivity than MORN. Additional work is needed to understand endothelial function differences among chronotypes to optimize cardiovascular disease risk reduction.

Atrial septal defect closure in children at young age is beneficial for left ventricular function.

Atrial septal defects (ASDs) lead to volume-loaded right ventricles (RVs). ASD closure does not always alleviate symptoms or improve exercise capacity, which is possibly explained by impaired left ventricular (LV) haemodynamics. This study evaluated the effect of ASD closure in children using non-invasive LV pressure-volume (PV) loops derived from cardiac magnetic resonance (CMR) imaging and brachial blood pressure, compared with controls. Twenty-three children with ASD underwent CMR, and 17 of them were re-examined 7 (6-9) months after ASD closure. Twelve controls were included. Haemodynamic variables were derived from PV loops by time-resolved LV volumes and brachial blood pressure. After ASD closure, LV volume increased [76 (70-86) vs. 63 (57-70) mL/m2, P = 0.0001]; however, it was still smaller than in controls [76 (70-86) vs. 82 (78-89) mL/m2, P = 0.048]. Compared with controls, children with ASD had higher contractility [2.6 (2.1-3.3) vs. 1.7 (1.5-2.2) mmHg/mL, P = 0.0076] and arterial elastance [2.1 (1.4-3.1) vs. 1.4 (1.2-2.0) mmHg/mL, P = 0.034]. After ASD closure, both contractility [2.0 (1.4-2.5) mmHg/mL, P = 0.0001] and arterial elastance [1.4 (1.3-2.0) mmHg/mL, P = 0.0002] decreased. Despite the left-to-right atrial shunt that leads to low LV filling and RV enlargement, the LV remains efficient and there is no evidence of impaired LV haemodynamics in children. Closure of ASD at young age while the ventricle is compliant is thus beneficial for LV function. LV volumes, however, remain small after ASD closure, which may impact long-term cardiovascular risk and exercise performance.

Application of an echocardiographic index to characterize right ventricular-pulmonary arterial coupling in heart failure.

Heart failure (HF), with its high morbidity and mortality, remains a global public health issue. Right ventricular (RV) dysfunction is a sign of deterioration in the natural history of HF, and a thorough evaluation of the relationship between RV contractility and its afterload through RV-pulmonary arterial (RV-PA) coupling can aid in accurately assessing overall RV function. The ratio of RV end-systolic elastance (Ees) to pulmonary arterial elastance (Ea) invasively measured by right heart catheterization served as the gold standard for evaluating RV-PA coupling. An echocardiographic index termed tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) has been shown to correlate well with Ees/Ea. TAPSE/PASP is recognized as a non-invasive surrogate of RV-PA coupling and has been extensively studied in patients with HF. This review briefly describes the methods of assessing RV-PA coupling, mainly discussing echocardiography, summarizes the clinical utility of TAPSE/PASP in patients with different HF types, and provides an overview of the available literature.

Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study.

An increasing number of hypertensive persons travel to high altitude (HA) while using antihypertensive medications such as beta-blockers. Nevertheless, while hypoxic exposure initiates an increase in pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR), the contribution of the autonomic nervous system is unclear. In animals, beta-adrenergic blockade has induced pulmonary vasoconstriction in normoxia and exaggerated hypoxic pulmonary vasoconstriction (HPV) and both effects were abolished by muscarinic blockade. We thus hypothesized that in humans, propranolol (PROP) increases Ppa and PVR in normoxia and exaggerates HPV, and that these effects of PROP are abolished by glycopyrrolate (GLYC). In seven healthy male lowlanders, Ppa was invasively measured without medication, with PROP and PROP+GLYC, both at sea level (SL, 488m) and after a 3-week sojourn at 3454m altitude (HA). Bilateral thigh-cuff release manoeuvres were performed to derive pulmonary pressure-flow relationships and pulmonary vessel distensibility. At SL, PROP increased Ppa and PVR from (mean±SEM) 14±1 to 17±1mmHg and from 69±8 to 108±11 dyn s cm-5 (21% and 57% increase, P=0.01 and P<0.0001). The PVR response to PROP was amplified at HA to 76% (P<0.0001, P[interaction]=0.05). At both altitudes, PROP+GLYC abolished the effect of PROP on Ppa and PVR. Pulmonary vessel distensibility decreased from 2.9±0.5 to 1.7±0.2 at HA (P<0.0001) and to 1.2±0.2 with PROP, and further decreased to 0.9±0.2% mmHg-1 with PROP+GLYC (P=0.01). Our data show that beta-adrenergic blockade increases, and muscarinic blockade decreases PVR, whereas both increase pulmonary artery elastance. Future studies may confirm potential implications from the finding that beta-adrenergic blockade exaggerates HPV for the management of mountaineers using beta-blockers for prevention or treatment of cardiovascular conditions.

Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis

BackgroundInterventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. ObjectivesThis study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). MethodsThe investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. ResultsWith faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). ConclusionsInterventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.