Total Vascular Resistance Research Articles

Randomized, placebo-controlled trial on the renal and systemic hemodynamic effects of empagliflozin

IntroductionSodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes (DM2) and chronic kidney disease (CKD). A decrease in renal blood flow (RBF) with attenuation of glomerular hyperfiltration may contribute. We examined renal and systemic hemodynamic effects of SGLT2i in relevant patient categories. MethodsUsing a double-blind placebo controlled cross-over design we randomized patients with DM2 and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2 (n=16), patients with DM2 and eGFR 20-60 ml/min/1.73m2 (n=17) and patients with non-diabetic CKD and eGFR 20-60 ml/min/1.73m2 (n=16) to empagliflozin 10 mg daily or placebo for four weeks and crossed over to the opposite treatment after two-week washout. RBF was measured with 82Rubidium-positron emission-tomography/computed-tomography, GFR with 99mTechnetium-diethylene-triamine-pentaacetate-clearance. 24-hour blood pressure (BP) and total vascular resistance (TVR) were recorded using a Mobil-O-graph. ResultsCompared to placebo empagliflozin reduced RBF by 6% in the DM2-CKD group (p<0.001) with non-significant decreases of 4% in the DM2 group and 1% in the CKD group (p=0.29 and 0.72). Empagliflozin reduced GFR, BP and TVR in all groups, while renal vascular resistance (RVR) remained unchanged ConclusionEmpagliflozin reduced RBF in patients with DM2 and CKD, whereas GFR, BP and TVR were reduced in all groups. This pattern, together with a lack of reduction in RVR, suggests SGLT2i protect the glomerulus through combined pre-glomerular and post-glomerular effects.

Estimating pulmonary arterial remodeling via an animal-specific computational model of pulmonary artery stenosis.

Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable investigation into the hemodynamic impact and altered mechanics associated with PAS. In this study, a one-dimensional (1D) fluid dynamics model was used to simulate hemodynamics throughout the pulmonary arteries of individual animals. The geometry of the large pulmonary arteries was prescribed by animal-specific imaging, whereas the distal vasculature was simulated by a three-element Windkessel model at each terminal vessel outlet. Remodeling of the pulmonary vasculature, which cannot be measured in vivo, was estimated via model-fitted parameters. The large artery stiffness was significantly higher on the left side of the vasculature in the left pulmonary artery (LPA) stenosis group, but neither side differed from the sham group. The sham group exhibited a balanced distribution of total distal vascular resistance, whereas the left side was generally larger in the LPA stenosis group, with no significant differences between groups. In contrast, the peripheral compliance on the right side of the LPA stenosis group was significantly greater than the corresponding side of the sham group. Further analysis indicated the underperfused distal vasculature likely moderately decreased in radius with little change in stiffness given the increase in thickness observed with histology. Ultimately, our model enables greater understanding of pulmonary arterial adaptation due to LPA stenosis and has potential for use as a tool to noninvasively estimate remodeling of the pulmonary vasculature.

Comparison of arterial stiffness index predictors in perimenopausal and postmenopausal women

ABSTRACT The present cross-sectional study aimed to compare climacteric symptoms and arterial stiffness indices between perimenopausal and postmenopausal women. The study sample comprised 70 healthy female participants, including 27 perimenopausal (49.8 ± 3.8 years) and 43 postmenopausal (55.7 ± 4 years) individuals. Validated methods were used to assess physical activity level, quality of life, climacteric symptoms, and anthropometric data. Arterial stiffness parameters were measured using Mobil-O-Graph. Pulse wave velocity (PWV) had a higher mean in the postmenopausal group than in the perimenopause group [8.04 m/s (SD 0.79) vs 7.01 m/s (SD 0.78), p < .001). PWV was strongly correlated with peripheral (r = 0.619) and central (r = 0.632) Systolic Blood Pressure (SBP) in postmenopausal group and an even stronger correlation was observed in perimenopausal group (r = 0.779 pSBP and 0.782 cSBP). BMI was a risk predictor in the perimenopausal group contributing positively to increase Pulse Pressure Amplification (PPA) (0.458, p < .05). In postmenopausal women, heart rate (HR) was a stronger predictor for central SBP, cardiac output, and total vascular resistance, whereas perimenopausal women HR influenced central diastolic blood pressure and PPA. Vascular changes initiating during perimenopause may contribute to the development of cardiovascular pathologies in the postmenopausal period. Further research with larger, representative samples is warranted to corroborate these findings.

Extracorporeal Mechanical Circulatory Support after Pulmonary Thromboendarterectomy: Experience of One Center.

Pulmonary thromboendarterectomy (PTE) is the treatment for patients with chronic thromboembolic disease. In the immediate postoperative period, some patients may still experience life-threatening complications such as reperfusion lung injury, airway bleeding, and persistent pulmonary hypertension with consequent right ventricular dysfunction. These issues may require support with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or lung transplantation. This study aims to analyze our series of PTEs that require ECMO. A descriptive and retrospective analysis of all PTE performed at the Favaloro Foundation University Hospital was conducted between March 2013 and December 2023. A total of 42 patients underwent PTE with a median age of 47 years (interquartile range: 26-76). The incidence of patients with ECMO was 26.6%, of which 53.6% were veno-venous (VV) ECMO. Preoperatively, a low cardiac index (CI), high right and left filling pressures, and high total pulmonary vascular resistances (PVRs) were associated with ECMO with a statistically significant relationship. The hospital mortality was 11.9%, and the mortality in the ECMO group was 45.5%, with a statistically significant relationship. Veno-arterial ECMO has a worse prognosis than VV ECMO. Preoperatively, a low CI, high right and left filling pressures, and high total PVRs were associated with ECMO after PTE.

Impact of social isolation during COVID-19 on anthropometric data, quality of life, baseline physical activity and aortic pulse wave parameters in children and adolescents in two independent samples

BackgroundThe social restrictions resulting from the COVID-19 pandemic had a great impact on the routine of children and adolescents, with important consequences such as sleep, eating, and psychological/psychiatric disorders. Even though there are no studies on the subject, it is possible that these changes in habit and routine have also affected arterial stiffness (AS) in this population, which is an important predictor of cardiovascular risk. This study aimed to assess possible changes in AS, anthropometry, and quality of life (QoL) resulting from the COVID-19 pandemic in children and adolescents.MethodsA controlled observational cross-sectional study was performed with 193 children and adolescents aged 9 to 19 years, allocated into two groups: before the pandemic (BPG) and one year after the pandemic (APG), matched by age and sex. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main AS indices evaluated were the augmentation index (AIx) and pulse wave velocity (PWV) derived from the aortic pulse wave. QoL was assessed using the Paediatric Quality of Life Inventory version 4.0 (PedsQL 4.0).ResultsRegarding QoL, the APG showed a worsening in emotional (p = 0.002) and school-related (p = 0.010) aspects. There was no statistically significant difference for most anthropometric parameters, except for the hip circumference, which was higher in the APG group (p < 0.001). The main predictor of AS in the paediatric population, AIx@75, was shown to be increased in the APG group (p < 0.001). Other cardiovascular parameters were also different, such as peripheral (p = 0.002) and central (p = 0.003) diastolic blood pressure, stroke volume (p = 0.010), and total vascular resistance (p = 0.002), which were shown to be decreased in the APG group, while the heart rate was increased (p < 0.001).ConclusionsOur results show that routine changes resulting from the period of social isolation increased cardiovascular risk in children and adolescents, evident by the increase in AIx@75, which is considered to be an important marker of cardiovascular risk in the paediatric population.

Abstract 12249: Activation of Prostaglandin E Receptor 4 Ameliorates Perivascular Inflammation and Pulmonary Hypertension in Rats

Introduction: Perivascular inflammation is involved in the progression of vascular remodeling and pulmonary arterial hypertension (PAH). Activation of prostaglandin E receptor 4 (EP 4 ) has recently been reported to reduce inflammation in ulcerative colitis and osteoarthritis, but there are no reports on perivascular inflammation in PAH. Hypothesis: EP 4 agonist ameliorate perivascular inflammation, vascular remodeling and pulmonary hypertension (PH). Methods and Results: We investigated the effects of EP 4 agonist (KAG-308) on hemodynamics and pulmonary artery remodeling in a monocrotaline (MCT)-exposed rat model of PH. Immunohistochemistry detected predominant expression of EP4 proteins in the macrophages and endothelial layer of pulmonary arteries in the lungs of normal and MCT-exposed rats. Compared to normal rats, MCT-exposed rats had increased nuclear factor kappa B (NFκB) activation and significantly higher interleukin 6 ( IL -6) mRNA levels (1.0±0.4 vs 62.3±39.7, p &lt; 0.05) in the lungs, and showed elevated right ventricular systolic pressure (RVSP; 29.7±1.8 vs 81.0±18.5 mmHg, p &lt; 0.0001), total pulmonary vascular resistance index (TPRI; 91.0±12.1 vs 161.4 ± 37.0 mmHg/mL/min/g, p &lt; 0.001) and RV hypertrophy (0.32±0.02 vs 0.57±0.10, p &lt; 0.0001), together with medial wall thickening and perivascular macrophage accumulation on day 21 after MCT injection. Oral administration of EP 4 agonist KAG-308 (1 mg/kg, twice daily, by gavage, day 0 to 21) significantly reduced NFκB activation and interleukin-6 mRNA levels (6.8 ± 2.5, p &lt; 0.05) in the lungs. Furthermore, KAG-308 prevented the elevated RVSP (53.1 ± 9.3 mmHg, p &lt; 0.01), TPRI (112.0 ± 16.6 mmHg/mL/min/g, p &lt; 0.05) and RV hypertrophy (0.47 ± 0.04, p &lt; 0.05) by inhibiting medical wall thickening and macrophage accumulation. Conclusion: EP 4 agonist ameliorated inflammation, vascular remodeling and PH in MCT-exposed rat. The EP 4 agonist KAG-308 is a potential therapeutic agent for the treatment of PAH.

The effect of prone positioning on maternal haemodynamics and fetal wellbeing in the third trimester-A primary cohort study with a scoping review.

Supine sleep position is associated with stillbirth, likely secondary to inferior vena cava compression, and a reduction in cardiac output (CO) and uteroplacental perfusion. Evidence for the effects of prone position in pregnancy is less clear. This study aimed to determine the effect maternal prone position on maternal haemodynamics and fetal heart rate, compared with left lateral position. Twenty-one women >28 weeks' gestation underwent non-invasive CO monitoring (Cheetah) every 5 minutes and continuous fetal heart rate monitoring (MONICA) in left lateral (20 minutes), prone (30 minutes), followed by left lateral (20 minutes). Anxiety and comfort were assessed by questionnaires. Regression analyses (adjusted for time) compared variables between positions. The information derived from the primary study was used in an existing mathematical model of maternal circulation in pregnancy, to determine whether occlusion of the inferior vena cava could account for the observed effects. In addition, a scoping review was performed to identify reported clinical, haemodynamic and fetal effects of maternal prone position; studies were included if they reported clinical outcomes or effects or maternal prone position in pregnancy. Study records were grouped by publication type for ease of data synthesis and critical analysis. Meta-analysis was performed where there were sufficient studies. Maternal blood pressure (BP) and total vascular resistance (TVR) were increased in prone (sBP 109 vs 104 mmHg, p = 0.03; dBP 74 vs 67 mmHg, p = 0.003; TVR 1302 vs 1075 dyne.s-1cm-5, p = 0.03). CO was reduced in prone (5.7 vs 7.1 mL/minute, p = 0.003). Fetal heart rate, variability and decelerations were unaltered. However, fetal accelerations were less common in prone position (86% vs 95%, p = 0.03). Anxiety was reduced after the procedure, compared to beforehand (p = 0.002), despite a marginal decline in comfort (p = 0.04).The model predicted that if occlusion of the inferior vena cava occurred, the sBP, dBP and CO would generally decrease. However, the TVR remained relatively consistent, which implies that the MAP and CO decrease at a similar rate when occlusion occurs. The scoping review found that maternal and fetal outcomes from 47 included case reports of prone positioning during pregnancy were generally favourable. Meta-analysis of three prospective studies investigating maternal haemodynamic effects of prone position found an increase in sBP and maternal heart rate, but no effect on respiratory rate, oxygen saturation or baseline fetal heart rate (though there was significant heterogeneity between studies). Prone position was associated with a reduction in CO but an uncertain effect on fetal wellbeing. The decline in CO may be due to caval compression, as supported by the computational model. Further work is needed to optimise the safety of prone positioning in pregnancy. This trial was registered at clinicaltrials.gov (NCT04586283).

Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (PH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. Retrospective study of 401 consecutive patients undergoing PEA at our institution between August2005 and March2020 was performed. Primary outcome was the need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. Females (N =203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p<0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p<0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final total pulmonary vascular resistance after PEA, 437Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p<0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p=0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs 89.9% in males at 5 years, p<0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p=0.04). Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients are important. Further investigations into possible mechanisms to explain the differences are warranted.

The First Local Experience of Use of Extracorporeal Circulatory Support with PROTEKDuo Dual-Lumen Cannula in a Patient with Acute Right Ventricular Failure

Acute right ventricular failure is a life-threatening condition that can occur as a result of a sudden increase in total pulmonary vascular resistance, in particular, as a result of pulmonary embolism. Most patients with thromboembolism are treated with thrombolytic therapy, but in some cases open thrombextraction is preferred. Removal of blood clots from the pulmonary vascular bed and cardiopulmonary bypass can lead to spasm of the pulmonary artery and to the elevation of total pulmonary resistance, which, in turn, increases the afterload on the right ventricle and can lead to a dramatic decrease in its mechanical function.&#x0D; The aim. The aim of this report is to present the first experience of using the right ventricular bypass with the PROTEKDuo cannula for the purpose of temporary mechanical support of the right ventricle.&#x0D; Case presentation. We studied a 63-year-old patient who underwent Studer technique for bladder adenocarcinoma. On the 14th day an acute massive pulmonary embolism occurred with a drop in hemodynamics and the presence of a floating clot on the right atrium. Thrombolysis carried significant risks due to possible bleeding and clot fragmentation in the right atrium with subsequent embolization of the pulmonary arteries. In these circumstances, open thrombectomy under hypothermic arrest was performed. Intraoperatively, the patient developed acute right ventricular failure resistant to all conservative therapy, therefore, right ventricular bypass was connected using PROTEKDuo, which made it possible to overcome the phenomena of acute right ventricular failure in the postoperative period.&#x0D; Conclusions. Our experience with right ventricular bypass using the PROTEKDuo dual-lumen cannula demonstrates another useful option for saving patients with isolated right ventricular failure.

PRELIMINARY DATA ON THE ENDOGENOUS OUABAIN IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION PATIENTS

Objective: The aim is to detect the endogenous ouabain (EO) in idiopathic pulmonary arterial hypertension (IPAH) patients. Design and method: EO is a steroid hormone secreted by the adrenal glands associated with adverse cardiovascular outcomes. However, EO plays other roles as brain protection against traumatic injury and seems involved in the adaptive response to hypoxia. Recently, we detected, for the first time, EO in a healthy human group of acute hypoxia (elite apnea divers) and in diving animals (common bottlenose dolphins, phocids and otariids, and loggerhead sea turtles). This study complements the above as we considered a human model of chronic hypoxia. We collected blood samples from five Caucasian males and measured EO with a Scintillation Proximity Assay. Results: We found that IPAH patients had higher plasma concentrations levels of EO than control subjects. In addition, EO plasma concentrations were negatively correlated with the mean pulmonary arterial pressure and total pulmonary vascular resistance (p-values &lt;0.05). A positive correlation trend was observed with the cardiac index, a marker of healthy cardiac output. The results could suggest that high concentrations of EO are predictive of a better adaptation of the right ventricular afterload. Conclusions: Although these are preliminary results, they match data coming from other studies on clinical conditions that frequently occur in comorbidity with IPAH. It can represent a helpful hint for future investigations involving other pathological conditions for possible therapeutic and diagnostic approaches.

The effects of nordic walking, high-intensity interval training, and moderate-to-vigorous intensity continuous training on arterial stiffness in patients with coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The investigator-initiated research was supported by the Innovations Fund of the Alternate Funding Plan for the Academic Health Sciences Centres of the Ministry of Ontario (PIs: Pipe, Reed) and Heart and Stroke Foundation of Canada (PI: Reid). Background Coronary artery disease (CAD) is a leading cause of mortality worldwide. Arterial stiffness, a process associated with aging, arteriosclerosis, and arterial remodeling, is a strong and independent predictor of cardiovascular and all-cause mortality in patients with CAD. Moderate-to-vigorous intensity continuous training (MICT) has been shown to improve arterial stiffness parameters, including pulse wave velocity (PWV, i.e., the speed at which arterial pressure waves travel along the aorta and large arteries) and augmentation index (AIx: i.e., aortic pressure waveform) in the CAD population. Yet, the role of alternative exercise training approaches on arterial stiffness in patients with CAD has not been elucidated. Our recent study demonstrated greater improvements following Nordic walking (NW) compared to high-intensity interval training (HIIT) and MICT in functional capacity, quality of life, and depression severity in patients with CAD. No previous trial has compared the efficacy of NW, HIIT, and MICT in improving arterial stiffness in patients with CAD. Alternatives to traditional MICT, such as NW and HIIT, may provide superior understudied benefits on vascular health in patients with CAD. Purpose We compared the effects of 12 weeks of NW, HIIT, and MICT on arterial stiffness in patients with CAD. Methods Patients with CAD were randomly assigned to: (1) NW (walking with NW poles at a resting heart rate [RHR] + 20–40 bpm), (2) HIIT (aerobic exercise equipment: 4 × 4-min of high-intensity work periods at 85%–95% peak HR), or (3) MICT (aerobic exercise equipment: RHR + 20–40 bpm) twice weekly for 12 weeks. At baseline and week 12, aortic stiffness parameters were measured using a non-invasive device by stroke volume (SV), total vascular resistance (TVR), AIx with and without normalization for a HR of 75 bpm (AIX@75), and PWV. Linear mixed-effects models with repeated measures were used to compare groups over time. Results A total of 130 patients with CAD (aged 61 ± 7 years; male: 85%) were randomized to NW (n = 43), HIIT (n = 43), or MICT (n = 44). Table 1 shows that significant main effects of time were observed for SV (∆: 5.485 m/L, F = 8.530, p = 0.004), with a time × group interaction (F = 3.710, p = 0.027) revealing a greater improvement in SV following NW compared to HIIT (F = 5.748, p = 0.019) and MICT (F = 5.494, p = 0.022). A significant time × group interaction (F = 3.700, p = 0.028) was observed in AIx@75, with a greater reduction following NW than MICT (F = 7.388, p = 0.008). No significant differences were observed in TVR, AIx, and PWV. Conclusion Our findings show that NW facilitated greater improvements in SV and AIx@75 parameters of arterial stiffness, an important predictor of future cardiovascular events, when compared to HIIT and MICT in patients with CAD. NW may be considered as an alternative exercise training to improve vascular health in those with CAD.

The prediction of hypertensive disorders by maternal hemodynamic assessment in the first trimester of pregnancy

Background Hypertensive disorders of pregnancy and fetal growth restriction share common etiopathological origins and could be caused by maternal hemodynamic maladaptation to pregnancy. Objective The aim of our study is to evaluate if there is a correlation between maternal hemodynamic detected by UltraSonic Cardiac Output Monitor (USCOM®) during the first trimester and the pregnancy outcome. Study design We recruited a nonconsecutive series of women in the first trimester of pregnancy with no previous history of hypertensive disorders. We measured the pulsatility index uterine arteries and performed a hemodynamic evaluation by USCOM® device. After delivery, we reported the development of hypertensive disorders or intrauterine fetal growth restriction later during gestation. Results A total of 187 women were enrolled during the first trimester; 17 (9%) developed gestational hypertension or preeclampsia while 11 (6%) delivered a restricted growth fetus. Mean uterine artery pulsatility index above the 95th percentile was significantly more frequent in both women who developed hypertension and those with fetal growth restriction compared to controls. Hemodynamic parameters (reduced cardiac output and increased total vascular resistance) were significantly different in the group that developed hypertensive disorders, compared to uncomplicated pregnancy. ROC curves demonstrated the usefulness of uterine artery pulsatility index in the prediction of fetal growth restriction, while hemodynamic parameters were significantly associated to the development of hypertensive disorders. Conclusions Hemodynamic maladaptation to pregnancy may predispose to the development of hypertension, while we demonstrated a significative relationship between growth restriction and mean uterine pulsatility index. Further studies are needed to assess the value of hemodynamics evaluation in screening protocols of preeclampsia.

Factors associated with arterial stiffness assessed by pulse pressure amplification in healthy children and adolescents: a cross-sectional study

BackgroundIncreasing evidence suggests that reducing pulse pressure amplification (PPA) plays an important role in pathogenesis and progression of cardiovascular disease. This is a cross-sectional, observational, and analytical study in which we evaluated the associated factors with a greater chance of reducing PPA in 136 healthy children and adolescents aged 8 to 19 years old stratified by gender and age group.MethodsArterial stiffness and vascular and hemodynamic parameters were non-invasively measured using Mobil-O-Graph® (IEM, Stolberg, Germany), a cuff-based oscillometric device. PPA was expressed as the peripheral-to-central pulse pressure ratio (PPp / PPc). Participants with PPA < 1.49 were considered as part of the arterial stiffness group.ResultsIn a univariate model, the increase in total vascular resistance, the reflection coefficient and the augmentation pressure were more likely to have arterial stiffness in all groups. The factors most likely to have arterial stiffness (as assessed by the reduction of the PPA) in the multivariate model were increasing age, the reflection coefficient and cardiac index in the total sample, male group and child and adolescent groups. In addition to age in the female group, cardiac output, stroke volume, and AIx@75 were the factors most likely to present arterial stiffness.ConclusionsThe results show for the first time in children and adolescents that the factors most likely to reduce PPA are related to the reflection wave, which determines aortic pressures and, therefore, left ventricular afterload.

The Impact of Left Ventricular Performance and Afterload on the Evaluation of Aortic Valve Stenosis: A 1D Mathematical Modeling Approach.

The transaortic valvular pressure gradient (TPG) plays a central role in decision-making for patients suffering from severe aortic stenosis. However, the flow-dependence nature of the TPG makes the diagnosis of aortic stenosis challenging since the markers of cardiac performance and afterload present high physiological interdependence and thus, isolated effects cannot be measured directly in vivo. We used a validated 1D mathematical model of the cardiovascular system, coupled with a model of aortic stenosis, to assess and quantify the independent effect of the main left ventricular performance parameters (end-systolic (Ees) and end-diastolic (Eed) elastance) and principal afterload indices (total vascular resistance (TVR) and total arterial compliance (TAC)) on the TPG for different levels of aortic stenosis. In patients with critical aortic stenosis (aortic valve area (AVA) ≤ 0.6 cm2), a 10% increase of Eed from the baseline value was associated with the most important effect on the TPG (-5.6 ± 0.5 mmHg, p < 0.001), followed by a similar increase of Ees (3.4 ± 0.1 mmHg, p < 0.001), in TAC (1.3 ±0.2 mmHg, p < 0.001) and TVR (-0.7 ± 0.04 mmHg, p < 0.001). The interdependence of the TPG left ventricular performance and afterload indices become stronger with increased aortic stenosis severity. Disregarding their effects may lead to an underestimation of stenosis severity and a potential delay in therapeutic intervention. Therefore, a comprehensive evaluation of left ventricular function and afterload should be performed, especially in cases of diagnostic challenge, since it may offer the pathophysiological mechanism that explains the mismatch between aortic severity and the TPG.

Exploratory study on the endogenous ouabain in idiopathic pulmonary arterial hypertension patients.

Endogenous ouabain (EO) is a steroid hormone secreted by the adrenal glands associated with adverse cardiovascular outcomes. However, EO plays other roles as brain protection against traumatic injury and seems involved in the adaptive response to hypoxia. Recently, we detected, for the first time, EO in a healthy human group of acute hypoxia and diving animals. This study complements the above as we considered a human model of chronic hypoxia. The aim is to detect EO in five idiopathic pulmonary arterial hypertension patients. We found that these patients had higher plasma concentrations of EO than control subjects. In addition, EO plasma concentrations were negatively correlated with the mean pulmonary arterial pressure and total pulmonary vascular resistance. The results could suggest that high concentrations of EO are predictive of better adaptation of the right ventricular afterload. Although the results are preliminary, they can represent a helpful hint for future investigations for possible therapeutic and diagnostic approaches.

S-15-5: GAPS AND ADVANCES FOR THE PREVENTION OF HYPERTENSION IN AFRICA: INSIGHTS FROM THE EXAMIN YOUTH SA STUDY

Paediatric hypertension is becoming a global health problem which is paralleled by overweight and obesity in children and adolescents, and tracks into adulthood. Therefore, promoting primary prevention of hypertension at early ages will reduce the increasing trends of hypertension in Africa. The prevalence of hypertension in South African children ranges between 7.5% and 22.3%, while care and treatment of hypertension remains a major challenge and health crisis. From the Exercise, Arterial Modulation and Nutrition in Youth South Africa (ExAMIN Youth SA) study using the latest 2017 American Academy of Pediatrics Clinical Practice Guidelines, we reported unique sex and ethnic differences of blood pressure (BP) in 5–9 year old children (n = 1062) and identified 14.1% children with elevated BP and almost 23% within the range of stage 1 or 2 hypertension. We also reported that 15.2% of the children were overweight and 4.4% obese according to the age and sex standardized body mass index (BMI) z-scores. Overweight and obesity were more prevalent in white children, while diastolic BP and total vascular resistance were higher in black children. The odds of having elevated BP were 60% higher with every standard deviation increase of BMI z-score. We analysed cortisol reactivity in relation to physical fitness to underpin the role of environmental stressors and physiological responses after inducing physical stress. We showed that white children had lower cardiorespiratory fitness (CRF) compared to children of African ancestry. However, African children had lower cortisol reactivity and unfavourable lower morning cortisol levels compared to white children. We demonstrated that lower CRF and higher BP are associated with lower cortisol responses in young children. In the same children and in comparison with a Swiss cohort, we investigated the role of high BP, obesity and ethnicity on retinal microvascular phenotype. We reported that obesity, hypertension and African ancestry are the main factors contributing to arteriolar narrowing. Since the microvasculature is also well represented by the kidneys, and the kidneys regulate BP, we also analysed a marker of proximal tubular function, alpha-1 microglobulin (A1 M), to identify early pathways of hypertension development in children. A1 M levels increased with higher BP, especially in children of African ancestry. With childhood lifestyle and behavioural risk factors being the most important for the prediction of cardiovascular events in adulthood, we argue that targeting health behaviour and optimising health education in early life are the most promising prospects to prevent early cardiovascular disease development in Africa.

S-57-3: GUT MICROBIAL METABOLITES LOWER 24-HOUR SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS

Objective: Clinical evidence supports that dietary fibre intake lowers blood pressure (BP). Dietary fibres remain intact until they reach the colon. There, they are fermented by gut microbial communities to produce metabolites, particularly short-chain fatty acids (SCFAs). Previous studies, including our own, have demonstrated that supplementation with the SCFAs acetate and butyrate lower BP in experimental models. However, whether dietary supplementation with SCFAs in humans elicits the same reduction in BP is undetermined. We aimed to establish whether a SCFAs-enriched dietary supplement lowers 24-hour BP in participants with essential hypertension. Design and method: Twenty untreated hypertensive participants, diagnosed by 24-hour BP using a Mobil-O-Graph device, were recruited for a phase II randomized placebo-controlled double-blind crossover trial. Participants were randomized to receive a daily intervention of 40 g/day of acetylated and butyrylated high amylose maize starch (HAMSAB) or 40 g/day of regular flour or cornflour (placebo). The dietary intervention lasted three weeks, with a three-week washout period following completion. The primary endpoint was a change in 24-hour systolic BP. Secondary endpoints included SCFA levels and changes in gut microbiome. Results: Participants were on average 55.8 ± 11.2 (mean ± SD) years of age, had a body mass index (BMI) of 25.7 ± 2.5km2/m, and 30% were female. The baseline 24-hour systolic BP was 136 ± 6mmHg. The dietary intervention was well-tolerated and had high acceptability with 93% compliance. There was no difference in 24-hour systolic BP between the baseline visits (P = 0.55) and the placebo (P = 0.18). After 3-weeks on the HAMSAB diet, the placebo-subtracted treatment 24-hour systolic BP difference was 6.1 ± 9.9mmHg (P = 0.027). These observations were independent of age, sex, BMI and study arm. Day and night systolic BP were reduced by 6.5 ± 12.3mmHg (P = 0.01) and 5.7 ± 9.8mmHg (P = 0.02), respectively, and 24-h central BP by 7.2 ± 14.7 mmHg (P = 0.005). There was no change in stroke volume, cardiac output or heart rate; however, HAMSAB reduced total vascular resistance (P = 0.049). Compared to the placebo, the HAMSAB diet elevated acetic and butyric acid levels by 7.8-fold (P = 0.016). HAMSAB also shifted the gut microbial ecosystem (P = 0.037) and increased the prevalence of the acetate and butyrate producers Parabacteroides distasonis and Ruminococcus gauvreauii (q-value &lt; 0.05). Conclusions: We observed a clinically relevant reduction in 24-hour systolic BP in participants with essential hypertension treated with the gut microbial-derived metabolites acetate and butyrate. These metabolites may represent a novel option for lowering BP. Low fibre diets and reduced gut microbial metabolites may be one of the principal reasons for the hypertension epidemic in Western countries.

Maternal hemodynamic profile during pregnancy and in the post-partum in hypertensive disorders of pregnancy and fetal growth restriction

Maternal cardiovascular changes, occurring since the beginning of pregnancy, are necessary for normal placentation and regular evolution of pregnancy. This study aimed to compare the hemodynamic profiles and cardiac remodeling of women with hypertensive disorders of pregnancy and either appropriate for gestational age fetuses or growth-restricted fetuses, women with normotensive pregnancies complicated by fetal growth restriction, and women with uncomplicated pregnancies, during pregnancy and the postpartum period. A prospective longitudinal case-control design was used for this study. Over the study period, 220 eligible women with singleton pregnancies were selected for the analysis and divided into 4 groups: (1) hypertensive disorders of pregnancy with appropriate for gestational age fetuses; (2) hypertensive disorders of pregnancy with fetal growth restriction; (3) normotensive fetal growth restriction; and (4) controls. Ultrasound fetal biometry and fetoplacental Doppler velocimetry were performed at recruitment. Maternal hemodynamic assessment using transthoracic echocardiography was performed at the time of recruitment by a dedicated cardiologist blinded to maternal clinical data. The same assessments were performed in 104 patients at 32 weeks (interquartile range, 24-40) after delivery by the same cardiologist. During pregnancy, women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction group showed significantly lower cardiac output and increased compared with those in the control group. These values were associated with concentric remodeling of the left ventricle owing to relatively increased wall thickness, which was not accompanied by an increase in left ventricular mass. Isolated fetal growth restriction presented similar but less important hemodynamic changes; however, there was no change in relative wall thickness. At postpartum follow-up, the hemodynamic parameters of women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and isolated-fetal-growth-restriction groups reverted to values similar to those of the control group. Only 8.3% of women in these groups experienced hypertension even in the postpartum period, and asymptomatic stage-B cardiac failure was observed for 17% at echocardiography. In the group of women with hypertensive disorders of pregnancy and appropriate for gestational age fetuses, cardiac output increased as in normal pregnancies, but total vascular resistance was significantly higher; hypertension then occurred, along with ventricular concentric hypertrophy and diastolic dysfunction. At postpartum follow-up, women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed significantly higher mean arterial pressure, total vascular resistance, and left ventricular mass compared with those in the control group. Persistent hypertension and asymptomatic stage-B cardiac failure were observed in 39.1% and 13% of women in the former group, respectively. Pregnancies with hypertensive disorders of pregnancy and fetal growth restriction and normotensive pregnancies with fetal growth restriction were associated with the hemodynamic profile of lower heart rate and cardiac output, most likely because of abnormal adaptation to pregnancy, as confirmed by abnormal changes from pregnancy to the postpartum period. The heart rates and cardiac output of women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed changes opposite to those observed in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and fetal-growth-restriction groups. Obesity and other metabolic risk factors, significantly prevalent in women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group, predispose to hypertension and cardiovascular diseases during pregnancy and the postpartum period, potentially offering a window for personalized prevention. Such preventive strategies could differ in women with hypertensive disorders of pregnancy and fetal growth restriction characterized by poor early placental development.

346 IMPACT OF EXERCISE-INDUCED PULMONARY HYPERTENSION ON THE RIGHT VENTRICLE AND WORSENING OF CARDIOVASCULAR RISK IN HIV PATIENTS

Abstract Background and Aim Exercise-induced pulmonary hypertension (ExPH), due to impaired pulmonary vascular and right ventricular contractile reserve on effort,predicts clinical outcomes, such as all-cause mortality or cardiovascular (CV) hospitalizations in patients with dyspnea on effort. We investigated its prognostic significance in HIV patients at risk for Pulmonary Arterial Hypertension (PAH). Methods In 52 consecutive HIV patients with either low (n=47) or intermediate probability (n=5) of PH at rest, we evaluated at time 0 and after 2 years the prognostic determinants of CV risk: onset or progression of heart failure/syncope; worsening of functional class; functional performance at the 6-Minute Walking Test and at cardiopulmonary exercise test (CPET); right atrial area; and pericardial effusion. We assigned a severity score 1-3 to each prognostic determinant, derived an overall CV risk score, and its 0-2 years change. Patients were classified as either at low, intermediate or high probability of ExPH at Stress Echocardiography (ESE), while ExPH at CPET was defined as absence of PH at rest, reduced peak VO2, VE/VCO2 &amp;gt;30 at anaerobic threshold, reduced O2 pulse, and ΔVO2/ΔW &amp;lt;9 mL/min/W. We then correlated ExPH at time 0 with clinical worsening (risk score increase &amp;gt;20% after 2 years). Results Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET, as well as in patients with intermediate/high compared to those with low probability of ExPH at ESE, who exhibited worse values of TAPSE and FAC (p&amp;lt;0.001 and p=0.01, respectively). A significant higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p&amp;lt;0.001), mPAP (p=0.004), higher TRV (p=0.006) as well as higher right atrial area (p&amp;lt;0.001) and indexed right atrial volume (p=0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and velocity-time integral at the level of right ventricular outflow tract) was higher in patients with ExPH as well as in patients with intermediate/high probability of ExPH (p&amp;lt;0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend towards clinical worsening compared to those with low probability of ExPH, albeit not statistically significant (p=0.137). In patients with low probability of ExPH, none had &amp;gt;20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p=0.048 at CPET, p=0.033 at ESE). Conclusions At short follow-up, ExPH is associated with a worsening trend in the CV risk score which, if confirmed after longer follow-up, could contribute to better risk stratification in HIV patients.

Impact of Exercise-Induced Pulmonary Hypertension on Right Ventricular Function and on Worsening of Cardiovascular Risk in HIV Patients.

Exercise-induced pulmonary hypertension (ExPH) predicts clinical outcomes, such as all-cause mortality and cardiovascular (CV) hospitalizations, in patients with dyspnea on effort. We investigated its prognostic significance in human immunodeficiency virus (HIV)-affected patients. In 52 consecutive HIV patients with either low (n = 47) or intermediate probability (n = 5) of PH at rest, we evaluated-at time 0 and after 2 years-the prognostic determinants of CV risk, according to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines. Patients were classified with or without ExPH at stress echocardiography (ESE) and cardiopulmonary exercise test (CPET). We then related ExPH at time 0 with clinical worsening (CV risk score increase &gt;20% after 2 years). Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET. This also occurred in patients with intermediate/high probability compared to those with low probability of ExPH at ESE. The former exhibited worse values of TAPSE and FAC (p &lt; 0.001 and p = 0.01, respectively). A significantly higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p &lt; 0.001), mPAP (p = 0.004) and higher TRV (p = 0.006), as well as higher right atrial area (p &lt; 0.001) and indexed right atrial volume (p = 0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and the velocity-time integral at the level of the right ventricular outflow tract) was higher both in patients with ExPH and in those with intermediate/high probability of ExPH (p &lt; 0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend (p = 0.137) towards clinical worsening compared to those with low probability of ExPH. No patients with low probability of ExPH had a &gt;20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p = 0.048 at CPET, p = 0.033 at ESE). The assessment of ExPH may predict a trend of increasing CV risk score over time. If confirmed at a longer follow-up, ExPH could contribute to better risk stratification in HIV patients.