Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. METHODS: One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. RESULTS: We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CONCLUSION: CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Renal arterial resistive index as a prognostic marker in lupus nephritis patients.

INTRODUCTION: Lupus nephritis (LN) is known to be one of the most serious complications of SLE and it is a major predictor of poor prognosis. Despite the improvement in understanding the pathophysiology of lupus nephritis and greater improvement in diagnostic approaches, lupus nephritis patients have poorer outcomes. OBJECTIVES: Study the relation between renal resistive index (RRI) and renal function and histopathological parameters in lupus nephritis (LN) patients. Also to investigate the usefulness of RRI in predicting response to treatment. PATIENTS AND METHODS: This study included 126 patients who were split into two groups (group 1: 101 LN patients and group 2: 25 SLE patients without renal affection); and 100 healthy controls (group 3). The RRI was measured for all participants through a colored Doppler ultrasound examination. LN patients underwent renal biopsy and received their therapy and were followed up for 6 months. RESULTS: The RRI was significantly greater in the LN group (mean±SD; 0.64±0.07) than in SLE patients without nephritis (0.5884±0.04) (P<0.0001). The RRI was greater in LN class IV (P<0.0001). RRI significantly correlated with the chronicity index (r=0.704, P<0.0001), activity index (r=0.310, P=0.002), and serum creatinine (r=0.607, P<0.0001) and negatively correlated with eGFR (r=-0.719, P<0.0001). Almost eighty-five percent (84.8%) of LN patients responded to induction therapy. RRI was significantly greater in the nonresponder group (mean±SD, 0.73±0.02) than that in the responder group (0.63±.07) (P<0.0001). All non-responders to induction therapy while only 29.8% of responders had an RRI of ˃0.7. RRI, according to regression analysis was a significant predictor of response to treatment in LN patients. CONCLUSION: RRI was significantly greater in the LN group and significantly correlated with kidney function and histopathological parameters. RRI can predict response to induction therapy in LN patients.

Impact of hyperaemic stenosis resistance on long-term outcomes of stable angina in the ILIAS Registry.

BACKGROUND: The hyperaemic stenosis resistance (HSR) index was introduced to provide a more comprehensive indicator of the haemodynamic severity of a coronary lesion. HSR combines both the pressure drop across a lesion and the flow through it. As such, HSR overcomes the limitations of the more traditional fractional flow reserve (FFR) or coronary flow reserve (CFR) indices. AIMS: We aimed to identify the diagnostic and prognostic value of HSR and evaluate the clinical implications. METHODS: Patients with chronic coronary syndromes (CCS) and obstructive coronary artery disease were selected from the multicentre ILIAS Registry. For this study, only patients with combined Doppler flow and pressure measurements were included. RESULTS: A total of 853 patients with 1,107 vessels were included. HSR more accurately identified the presence of inducible ischaemia compared to FFR and CFR (area under the curve 0.71 vs 0.66 and 0.62, respectively; p<0.005 for both). An abnormal HSR measurement was an independent and important predictor of target vessel failure at 5-year follow-up (hazard ratio 3.80, 95% confidence interval: 2.12-6.73; p<0.005). In vessels deferred from revascularisation, HSR seems to identify more accurately those vessels that may benefit from revascularisation rather than FFR and/or CFR. CONCLUSIONS: The present study affirms the theoretical advantages of the HSR index for the detection of ischaemia-Âinducing coronary lesions in a large CCS population. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry], ClinicalTrials.gov: NCT04485234).

Effects of age on microvascular function in patients with normal coronary arteries.

BACKGROUND: It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. AIMS: Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. METHODS: In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rµ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). RESULTS: The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rµ (Rµ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rµ (Rµ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). CONCLUSIONS: There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

Exercise pulmonary hypertension in patients with systemic sclerosis based on updated guidelines.

Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.

The association of right ventricular-pulmonary arterial coupling and pulmonary vascular resistance in adult patients with uncorrected atrial septal defect.

BACKGROUND: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. METHODS: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. RESULTS: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. CONCLUSION: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity.

Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI.

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

The resistive and pulsatility indices of the dorsal metatarsal artery for the screening of peripheral lower artery disease in patients with and without diabetes.

BACKGROUND: In lower extremity peripheral artery disease (PAD), the ankle-brachial index (ABI) is an easily reproducible diagnostic tool for PAD, but it loses reliability when > 1.4 due to calcification of the vessel wall. Patients with diabetes are at higher risk for wall calcification. In order to overcome the limitation and reliability of ABI, particularly in patients with diabetes, we decided to assess resistive (RI) and pulsatility index (PI) by ultrasound doppler of the dorsal metatarsal artery (DMA). RESULTS: We therefore analyzed 51 legs (32 patients), evaluating the correlation between PI, RI, and ABI. Patients with diabetes were 21 (65.6 %), accounting for 33 legs (64.7 %). Out of 51 legs assessed, 37 (72.5 %) cases had compressible arteries, whereas in 14 legs (27.5 %) ABI was not calculable due to wall calcification. PAD was significantly associated with lower both RI and PI of the DMA (both p < 0.000). RI, but not PI, showed a significant correlation (r = 0.535) with ABI, when ABI was less than 1.4, but not when ABI > 1.4. When analyzed separately, patients with diabetes showed a similar figure in comparison with those without diabetes (r = 0.600), RI, but not PI, showed a significant correlation with ABI. CONCLUSION: Dorsal metatarsal artery resistive index (MARI) showed a significant inverse correlation with PAD, similarly to ABI, irrespective of the presence of diabetes. MARI seems to be an effective screening tool for PAD even in patients with wall calcification. Further studies are needed for confirming the results of the present pilot study.

Angiography-versus wire-based microvascular resistance index to detect coronary microvascular obstruction associated with ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) measured by cardiac magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) has important prognostic implications. While invasive index of microvascular resistance (IMR) have been shown to predict the occurrence and extent of MVO, the role of the angiography-based microvascular resistance (Angio-IMR) for this purpose remains unknown. The present study aims to perform a head-to-head comparison of wire-based and angiography-derived microcirculatory resistance (IMR and Angio-IMR, respectively) for the detection of MVO. METHODS: Patients with a first STEMI and multivessel disease underwent CMR for detection of MVO, and angio-IMR and IMR measurements during PPCI and at 30 day follow up, both in STEMI culprit and non-culprit vessels. RESULTS: 58 patients were included (mean age 60.7 ± 9.9 years, 82% male). At the time of PPCI, angio-IMR and IMR exhibited significant correlation (r = 0.70, P < 0.001), and agreement (coefficient of agreement 0.58). Both indices showed good predictive value of MVO [Angio IMR: AUC 0.79 (95% CI: 0.667-0.928); IMR: AUC 0.70 (95% CI: 0.539-0.853); p = 0.15]. Angio-IMR 40 U and IMR 34 U were identified as best cut-offs for prediction of MVO. In non-culprit vessels, angio-IMR and IMR also correlated well (rho = 0.59, p < 0.001), with overall lower mean values compared to culprit vessels (Angio-IMR: 36 vs. 23; IMR: 39 vs. 22, p < 0.001 for both comparisons). CONCLUSION: Angio-IMR constitutes a valid alternative to wire-based IMR in predicting MVO in STEMI. Angio-IMR and IMR show a good correlation in the acute and subacute STEMI phases, both in culprit and non-culprit vessels.

Identifying problematic arteriovenous fistula with CFD-derived resistance: An exploratory study.

Arteriovenous fistula (AVF) is the optimal form of vascular access for most haemodialysis dependant patients; however, it is prone to the formation of stenoses that compromise utility and longevity. Whilst there are many factors influencing the development of these stenoses, pathological flow-related phenomena may also incite the formation of intimal hyperplasia, and hence a stenosis. Repeated CFD-derived resistance was calculated for six patient who had a radiocephalic AVF, treated with an interwoven nitinol stent around the juxta-anastomotic region to address access dysfunction. A three-dimensional freehand ultrasound system was used to obtain patient-specific flow profiles and geometries, before performing CFD simulations to replicate the flow phenomena in the AVF, which enabled the calculation of CFD-derived resistance. We presented six patient cases who were examined before and after treatment and our results showed a 77% decrease in resistance, recorded after a surgical intervention to address access dysfunction. Problematic AVFs were found to have high resistance, particularly in the venous segment. AVFs with no reported clinical problems, and clinical patency, had low resistance in the venous segment. There did not appear to be any relationship with clinical problems/patency and resistance values in the arterial segment. Identifying changes in resistance along the circuit allowed stenoses to be identified, independent to that determined using standard sonographic criteria. Our exploratory study reveals thatCFD-derived resistance is a promising metric that allows for non-invasive identification of diseased AVFs. The pipeline analysis enabled regular surveillance of AVF to be studied to aid with surgical planning and outcome, further exhibiting its clinical utility.

Insights into RC time curve fit analysis of pulmonary artery pressure decay.

The notion of a constant relationship between resistance and capacitance (RC time) in the pulmonary circulation has been challenged by more recent research. The RC time can be obtained using either a simplified empirical approach or a semilogarithmic equation. Although direct curve-fit analysis is a feasible and ostensibly reference approach for RC analysis, it remains largely unexplored. We aimed to study the relationship between various RC methods in different states of pulmonary hemodynamics. Methods In total, 182 patients underwent clinically indicated right heart catheterization. The pressure curves were exported and processed using the MATLAB software. We calculated the RC time using the empirical method (RCEST), semilogarithmic approach (RCSL), and direct measurement of curve fit (RCFIT). Results Among 182 patients, 137 had pulmonary hypertension due to left heart disease (PH-LHD), 35 had pulmonary arterial hypertension (PAH), and 10 demonstrated normal hemodynamics (non-PH). RCEST consistently overestimated the RCFIT and RCSL measurements by a mean of 75%. With all three methods, the RC values were longer in the PAH (RCFIT = 0.36 ± 0.14 s) than in the PH-LHD (0.27 ± 0.1 s) and non-PH (0.27 ± 0.09 s) groups (p < 0.001). Although the RCSL and RCFIT values were similar among the three subgroups, they exhibited broad limits of agreement. Finally, the RCEST demonstrated a strong discriminatory ability (AUC = 0.86, p < 0.001, CI = 0.79-0.93) in identifying PAH. Conclusion RC time in PAH patients was substantially prolonged compared to that in PH-LHD and non-PH patients. The use of the empirical formula yielded systematic RC overestimation. In contrast, the semilogarithmic analysis provided reliable RC estimates, particularly for group comparisons.

Rapid changes in cerebrovascular compliance during vasovagal syncope.

PURPOSE: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS. METHODS: Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16 years, mean body mass index: 24.9 ± 4.0 kg/m2) at supine rest and during HUT (80 degree angle). Individual ABP and CBV waveforms during VVS were input into a modified Windkessel model to calculate Ci and ohmic CVR. Gosling's pulsatility index (Pi; pulse amplitude/mean CBV) was calculated. RESULTS: Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12 mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13 mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R2 = 0.79, P < 0.01). Increased Ci contributed to changes in mean CBV (P < 0.01) but decreased CVR did not (P = 0.28). CONCLUSIONS: These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP.

The Impact of Microvascular Resistance Reserve on the Outcome of Patients With STEMI.

BACKGROUND: Microvascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined. OBJECTIVES: This study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR. METHODS: This prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization and returned at 3 months for coronary physiology assessments with bolus thermodilution. The prevalence of CMD (MRR <3) and the association between MRR and major adverse cardiovascular and cerebrovascular events (MACCEs) at 12 months were investigated. RESULTS: The median age of patients was 65 years, and 59.5% were men. At the 3-month follow-up, 56 patients (27%) had CMD (MRR <3.0). The number of MACCEs at 12 months was higher in patients with vs without CMD (48.2% vs 11.0%; P < 0.001). MRR was independently associated with 12-month MACCEs (HR: 0.45 per unit increase; 95% CI: 0.31-0.67; P < 0.001) and with stroke, heart failure, and poorer recovery in left ventricular systolic function. The areas under the receiver-operating characteristic curves for predicting MACCEs at 12 months with fractional flow reserve, coronary flow reserve (CFR), the index of microvascular resistance (IMR), and MRR were 0.609, 0.762, 0.781, and 0.743, respectively. The prognostic performance of CFR, IMR, and MRR were all comparable. CONCLUSIONS: The novel parameter MRR is a prognostic marker of MACCEs in STEMI patients with a comparable performance to CFR and IMR. (Impact of TMAO Serum Levels on Hyperemic IMR in STEMI Patients [TAMIR]; NCT05406297).

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study.

BACKGROUND AND AIMS: Microvascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). METHODS: In this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. RESULTS: Among 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). CONCLUSIONS: Our study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

In silico modelling of stroke volume, cardiac output and systemic vascular resistance in cardiovascular safety pharmacology studies by telemetry.

The principle of proportionality of the systolic area of the central aortic pressure to stroke volume (SV) has been long known. The aim of the present work was to evaluate an in silico solution derived from this principle for modelling SV (iSV model) in cardiovascular safety pharmacology studies by telemetry. Blood pressure was measured in the abdominal aorta in accordance with standard practice. Central aortic pressure was modelled from the abdominal aortic pressure waveform using the N-point moving average (NPMA) method for beat-to-beat estimation of SV. First, the iSV was compared to the SV measured by ultrasonic flowmetry in the ascending aorta (uSV) after various pharmacological challenges in beagle dogs anaesthetised with etomidate/fentanyl. The iSV showed minimal bias (0.2 mL i.e. 2%) and excellent agreement with uSV. Then, previous telemetry studies including reference vasoactive and inotropic compounds were retrospectively reanalysed to model drug effects on stroke volume (iSV), cardiac output (iCO) and systemic vascular resistance (iSVR). Among them, the examples of nicardipine and isoprenaline highlight risks of erroneous or biased estimation of drug effects from the abdominal aortic pressure due to pulse pressure amplification. Furthermore, the examples of verapamil, quinidine and moxifloxacin show that iSV, iCO and iSVR are earlier biomarkers than blood pressure itself for predicting drug effect on blood pressure. This in silico modelling approach included in vivo telemetry safety pharmacology studies can be considered as a New Approach Methodology (NAM) that provides valuable additional information and contribute to improving non-clinical translational research to the clinic.

A multi-objective optimisation approach for the linear modelling of cerebral autoregulation system.

OBJECTIVE: Dynamic cerebral autoregulation (dCA) has been addressed through different approaches for discriminating between normal and impaired conditions based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CF). This work presents a novel multi-objective optimisation (MO) approach for finding good configurations of a cerebrovascular resistance-compliance model. METHODS: Data from twenty-nine subjects under normo and hypercapnic (5% CO2 in air) conditions was used. Cerebrovascular resistance and vessel compliance models with ABP as input and CF velocity as output were fitted using a MO approach, considering fitting Pearson's correlation and error. RESULTS: MO approach finds better model configurations than the single-objective (SO) approach, especially for hypercapnic conditions. In addition, the Pareto-optimal front from the multi-objective approach enables new information on dCA, reflecting a higher contribution of myogenic mechanism for explaining dCA impairment.

Insulin resistance in the adipose tissue predicts future vascular resistance: The Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases.

BACKGROUND AND AIMS: Diameter, plaque score, and resistance index (RI) in the common carotid artery (CCA) are indicators of arterial remodeling, atherosclerosis, and vascular resistance, respectively. This study investigated the longitudinal association between adipose tissue insulin resistance or serum free fatty acid (FFA) levels and the CCA parameters. METHODS: This retrospective cohort analysis included 1089 participants (mean age 57.6 years; 40.0 % women) with data on health checkups from January 1982 to March 2003 and carotid artery ultrasonography from January 2015 to June 2019. Baseline serum FFA and immunoreactive insulin levels were assessed before and 30, 60, and 120 min after glucose ingestion. Adipose insulin resistance index (Adipo-IR) was calculated as the product of fasting serum insulin and FFA levels. An RI value >0.75 was defined as high RI. RESULTS: A significant association was found between Adipo-IR and RI; however, Adipo-IR showed no association with CCA diameter or plaque score. The incidence of high RI increased with Adipo-IR quartile (Q) groups (47.3 % in Q1, 52.8 % in Q2, 53.3 % in Q3, 62.4 % in Q4; Cochrane-Armitage test for trend, p < 0.001). In multivariate analysis, Adipo-IR levels (Q4 vs. Q1 odds ratio: 1.67, 95 % confidence interval: 1.12-2.51) were positively associated with high RI incidence. Moreover, a significant association was found between RI and serum FFA levels after glucose intake, but not fasting FFA levels. CONCLUSIONS: Future vascular resistance was predicted by insulin resistance in the adipose tissue. After glucose intake, serum FFA levels may significantly impact vascular resistance development.