Noninvasive Hemodynamic Assessment Research Articles

Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI

Background and objectiveThe evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. MethodsA complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. ResultsThe analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. ConclusionsThe findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Future of invasive and non-invasive hemodynamic assessment for coronary artery disease management.

Coronary artery disease represents a global health challenge. Accurate diagnosis and evaluation of hemodynamic parameters are crucial for optimizing patient management and outcomes. Nowadays a wide range of both non-invasive and invasive methods are available to assess the hemodynamic impact of both epicardial coronary stenosis and vasomotor disorders. In fact, over the years, important developments have reshaped the nature of both invasive and non-invasive diagnostic techniques, and the future holds promises for further innovation and integration. Non-invasive techniques have progressively evolved and currently a broad spectrum of methods are available, from cardiac magnetic resonance imaging with pharmacological stress and coronary computed tomography (CT) to the newer application of FFR-CT and perfusion CT. Invasive methods, on the contrary, have developed to a full-physiology approach, able not only to identify functionally significant lesions but also to evaluate microcirculation and vasospastic disease. The aim of this review is to summarize the current state-of-the-art of invasive and non-invasive hemodynamic assessment for CAD management.

Comprehensive non-invasive Hemodynamic Assessment in Acute Decompensated Heart Failure-Related Cardiogenic Shock. A step towards echodynamics.

Hemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of hemodynamics in acute decompensated heart failure-related CS (ADHF-CS). All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 minutes before RHC. The evaluated hemodynamic parameters and their echocardiographic estimates ("e") comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). 101 ADHF-CS patients (56±11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29±5%) were included. Good correlation was found for CI, systolic PAP, RAP and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r=0.67) and PVR (r=0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 l/min/m2) were 0.97 and 0.73 respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO<0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, p<0.001). Echocardiographic estimation of hemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation.

The Impact of COVID-19 during Pregnancy on Maternal Hemodynamic Function, Angiogenic Markers and Neonatal Outcome.

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in pregnancy are associated with the development of preeclampsia and fetal growth restriction (FGR). Recently, preeclampsia was linked to impaired maternal hemodynamic function. This retrospective study evaluated singleton pregnancies with COVID-19 during pregnancy and healthy pregnant controls matched for gestational age from November 2020 to March 2022. Non-invasive assessment of maternal hemodynamics by continuous wave Doppler ultrasound measurements (USCOM-1A® Monitor) and oscillometric arterial stiffness (Arteriograph) was performed. Overall, 69 pregnant women were included-23 women after COVID-19 during pregnancy and 46 healthy controls. While two women (8.7%) were admitted to the hospital due to COVID-19-related symptoms, none required intensive care unit admission or non-invasive/invasive ventilation. There were no statistically significant differences in the majority of hemodynamic parameters between the two cohorts. The prevalence of FGR was significantly higher in the COVID-19 during pregnancy group (9.5% vs. healthy controls: 0.0%; p = 0.036), especially in nulliparous women. No difference in angiogenic markers and neonatal outcomes were observed between pregnant women after COVID-19 and healthy controls. In conclusion, no significant differences in hemodynamic parameters or neonatal outcome were observed in women with COVID-19 during pregnancy. However, an increased prevalence of FGR could be described.

Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study

IntroductionTo evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction. Methods30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later. ResultsIn the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group. DiscussionThe combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment.

Non-invasive hemodynamic assessment in obese pregnant women compared with non-obese patients: A prospective studY

Non-invasive hemodynamic assessment in obese pregnant women compared with non-obese patients: A prospective studY

Advanced CT measures of coronary artery disease with intermediate stenosis in patients with severe aortic valve stenosis

BackgroundCoronary artery disease (CAD) and severe aortic valve stenosis (AS) frequently coexist. While pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) allows to rule out obstructive CAD, interpreting hemodynamic significance of intermediate stenoses is challenging. This study investigates the incremental value of CT-derived fractional flow reserve (CT-FFR), quantitative coronary plaque characteristics (e.g., stenosis degree, plaque volume, and composition), and peri-coronary adipose tissue (PCAT) density to detect hemodynamically significant lesions among those with AS and CAD.Materials and methodsWe included patients with severe AS and intermediate coronary lesions (20–80% diameter stenosis) who underwent pre-TAVR CTA and invasive coronary angiogram (ICA) with resting full-cycle ratio (RFR) assessment between 08/16 and 04/22. CTA image analysis included assessment of CT-FFR, quantitative coronary plaque analysis, and PCAT density. Coronary lesions with RFR ≤ 0.89 indicated hemodynamic significance as reference standard.ResultsOverall, 87 patients (age 77.9 ± 7.4 years, 38% female) with 95 intermediate coronary artery lesions were included. CT-FFR showed good discriminatory capacity (area under receiver operator curve (AUC) = 0.89, 95% confidence interval (CI) 0.81–0.96, p < 0.001) to identify hemodynamically significant lesions, superior to anatomical assessment, plaque morphology, and PCAT density. Plaque composition and PCAT density did not differ between lesions with and without hemodynamic significance. Univariable and multivariable analyses revealed CT-FFR as the only predictor for functionally significant lesions (odds ratio 1.28 (95% CI 1.17–1.43), p < 0.001). Overall, CT-FFR ≤ 0.80 showed diagnostic accuracy, sensitivity, and specificity of 88.4% (95%CI 80.2–94.1), 78.5% (95%CI 63.2–89.7), and 96.2% (95%CI 87.0–99.5), respectively.ConclusionCT-FFR was superior to CT anatomical, plaque morphology, and PCAT assessment to detect functionally significant stenoses in patients with severe AS.Clinical relevance statementCT-derived fractional flow reserve in patients with severe aortic valve stenosis may be a useful tool for non-invasive hemodynamic assessment of intermediate coronary lesions, while CT anatomical, plaque morphology, and peri-coronary adipose tissue assessment have no incremental or additional benefit. These findings might help to reduce pre-transcatheter aortic valve replacement invasive coronary angiogram.Key Points• Interpreting the hemodynamic significance of intermediate coronary stenoses is challenging in pre-transcatheter aortic valve replacement CT.• CT-derived fractional flow reserve (CT-FFR) has a good discriminatory capacity in the identification of hemodynamically significant coronary lesions.• CT-derived anatomical, plaque morphology, and peri-coronary adipose tissue assessment did not improve the diagnostic capability of CT-FFR in the hemodynamic assessment of intermediate coronary stenoses.

Pulmonary and Systemic Hemodynamics in Patients with Hyperthyroidism

BackgroundThere is an association between hyperthyroidism and pulmonary hypertension. However, the prevalence of pulmonary hypertension in hyperthyroidism and the underlying mechanisms are incompletely defined. MethodsConsecutive patients with severe hyperthyroidism, mostly due to Graves disease, were included in this single-center study. Echocardiographic assessment of pulmonary hemodynamics was performed at the time of hyperthyroidism diagnosis (baseline) and after normalization of thyroid hormones (follow-up; median 11 months). In a subset of patients, right heart catheterization and noninvasive assessment of central hemodynamics was performed. ResultsAmong all 99 patients, 31% had pulmonary hypertension at baseline. The estimated systolic pulmonary artery pressure correlated significantly with the estimated left ventricular filling pressure (E/e′). The invasively measured systolic pulmonary artery pressure correlated well with the estimated systolic pulmonary artery pressure. Cardiac output, E/e′, left and right ventricular dimensions were significantly reduced from baseline to follow-up, whereas the estimated pulmonary vascular resistance did not differ. Diastolic blood pressure was significantly higher at follow-up, with no change in systolic blood pressure. The central systolic blood pressure, however, exhibited a trend for a reduction at follow-up, while the pulse wave velocity was significantly lower at follow-up. ConclusionsApproximately one-third of patients with hyperthyroidism have evidence of pulmonary hypertension. Our data suggest that an increased cardiac output and left ventricular filling pressure are the main mechanisms underlying the elevated systolic pulmonary artery pressure in hyperthyroidism, whereas there is no evidence of significant pulmonary vascular disease.

4D Flow Patterns and Relative Pressure Distribution in a Left Ventricle Model by Shake-the-Box and Proper Orthogonal Decomposition Analysis

PurposeIntraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice.MethodsIn this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed.ResultsAs a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction.ConclusionsThis work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis.

Acute fetal cardiovascular adaptation to artificial placenta in sheep model.

To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non-invasive hemodynamic assessment. This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109-117 days' gestation. The study was designed to collect in-utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1-3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3-24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre- and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. Compared with in-utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06-1.50) vs 0.38 (IQR, 0.31-0.50) vs 0.36 (IQR, 0.29-0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41-0.67) vs 0.29 (IQR, 0.22-0.33) vs 0.36 (IQR, 0.22-0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18-22 cm/s) vs 39 cm/s (IQR, 31-43 cm/s) vs 43 cm/s (IQR, 34-54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35-54 mmHg), 72 mmHg (IQR, 61-77 mmHg) and 58 mmHg (IQR, 50-64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142-156 bpm) vs 188 bpm (IQR, 171-209 bpm) vs 175 bpm (IQR, 165-190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34-41%) in utero, 38% (IQR, 30-40%) at 30 min and 37% (IQR, 33-40%) at 180 min (P = 0.807 for extreme timepoints). Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short-term evaluation, cardiac structure and function were preserved. However, the system resulted in non-physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Application of non-invasive bioreactance to assess hemodynamic function in patients with hypertrophic cardiomyopathy.

Non-invasive technologies have become popular for the clinical evaluation of cardiac function. The present study evaluated hemodynamic response to cardiopulmonary exercise stress testing using bioreactance technology in patients with hypertrophic cardiomyopathy. The study included 29 patients with HCM (age 55 ± 15 years; 28% female) and 12 age (55 ± 14 years), and gender matched (25% female) healthy controls. All participants underwent maximal graded cardiopulmonary exercise stress testing with simultaneous non-invasive hemodynamic bioreactance and gas exchange. At rest, patients with HCM demonstrated significantly lower cardiac output (4.1 ± 1.3 vs. 6.1 ± 1.2 L/min; p < 0.001), stroke volume (61.5 ± 20.8 vs. 89.5 ± 19.8 mL/beat; p < 0.001), and cardiac power output (0.97 ± 0.3 vs. 1.4 ± 0.3watt; p < 0.001), compared to controls. At peak exercise, the following hemodynamic and metabolic variables were lower in HCM patients that is, heart rate (118 ± 29 vs. 156 ± 20 beats/min; p < 0.001), cardiac output (15.5 ± 5.8 vs. 20.5 ± 4.7 L/min; p = 0.017), cardiac power output (4.3 ± 1.6 vs. 5.9 ± 1.8 watts; p = 0.017), mean arterial blood pressure (126 ± 11 vs. 134 ± 10 mmHg; p = 0.039), and oxygen consumption (18.3 ± 6.0 vs. 30.5 ± 8.3 mL/kg/min; p < 0.001), respectively. Peak arteriovenous oxygen difference and stroke volume were not significantly different between HCM patients and healthy controls (11.2 ± 6.4 vs. 11.9 ± 3.1 mL/100 mL, p = 0.37 and 131 ± 50.6 vs. 132 ± 41.9 mL/beat, p = 0.76). There was a moderate positive relationship between peak oxygen consumption and peak heart rate (r = 0.67, p < 0.001), and arteriovenous oxygen difference (r = 0.59, p = 0.001). Functional capacity is significantly reduced in patients with HCM primarily due to diminished central (cardiac) rather than peripheral factors. Application of non-invasive hemodynamic assessment may improve understanding of the pathophysiology and explain mechanisms of exercise intolerance in hypertrophic cardiomyopathy.

Patient-specific computational simulation of coronary artery bypass grafting.

Coronary artery bypass graft surgery (CABG) is an intervention in patients with extensive obstructive coronary artery disease diagnosed with invasive coronary angiography. Here we present and test a novel application of non-invasive computational assessment of coronary hemodynamics before and after bypass grafting. We tested the computational CABG platform in n = 2 post-CABG patients. The computationally calculated fractional flow reserve showed high agreement with the angiography-based fractional flow reserve. Furthermore, we performed multiscale computational fluid dynamics simulations of pre- and post-CABG under simulated resting and hyperemic conditions in n = 2 patient-specific anatomies 3D reconstructed from coronary computed tomography angiography. We computationally created different degrees of stenosis in the left anterior descending artery, and we showed that increasing severity of native artery stenosis resulted in augmented flow through the graft and improvement of resting and hyperemic flow in the distal part of the grafted native artery. We presented a comprehensive patient-specific computational platform that can simulate the hemodynamic conditions before and after CABG and faithfully reproduce the hemodynamic effects of bypass grafting on the native coronary artery flow. Further clinical studies are warranted to validate this preliminary data.

Echocardiographic estimation of pulmonary vascular resistance in advanced lung disease.

Noninvasive assessment of pulmonary hemodynamics is often performed by echocardiographic estimation of the pulmonary artery systolic pressure (ePASP), despite limitations in the advanced lung disease population. Other noninvasive hemodynamic variables, such as echocardiographic pulmonary vascular resistance (ePVR), have not been studied in this population. We performed a retrospective analysis of 147 advanced lung disease patients who received both echocardiography and right heart catheterization for lung transplant evaluation. The ePVR was estimated by four previously described equations. Noninvasive and invasive hemodynamic parameters were compared in terms of correlation, agreement, and accuracy. The ePVR models strongly correlated with invasively determined PVR and had good accuracy with biases of <1 Wood units (WU), although with moderate precision and wide 95% limits of agreement varying from 5.9 to 7.8 Wood units. The ePVR models were accurate to within 1.9 WU in over 75% of patients. In comparison to the ePASP, ePVR models performed similarly in terms of correlation, accuracy, and precision when estimating invasive hemodynamics. In screening for pulmonary hypertension, ePVR models had equivalent testing characteristics to the ePASP. Mid-systolic notching of the right ventricular outflow tract Doppler signal identified a subgroup of 11 patients (7%) with significantly elevated PVR and mean pulmonary artery pressures without relying on the acquisition of a tricuspid regurgitation signal. Analysis of ePVR and determination of the notching pattern of the right ventricular outflow tract Doppler flow velocity envelope provide reliable insights into hemodynamics in advanced lung disease patients, although limitations in precision exist.

Non-invasive maternal hemodynamic assessment to classify high-risk pregnancies complicated by fetal growth restriction

Non-invasive maternal hemodynamic assessment to classify high-risk pregnancies complicated by fetal growth restriction

Non-invasive assessment of cerebral hemoglobin parameters in intracranial dural arteriovenous fistula using functional near-infrared spectroscopy-A feasibility study.

The purpose of this study was to assess the feasibility of non-invasive assessment of cerebral hemodynamics using functional near-infrared spectroscopy (fNIRS) in patients with intracranial dural arteriovenous fistula (DAVF) and to correlate the hemodynamic changes with definitive endovascular treatment. Twenty-seven DAVF patients and 23 healthy controls underwent 20-mins task-based functional near-infrared spectroscopy and neuropsychology evaluation. The mean change in the hemoglobin concentrations obtained from the prefrontal cortex was assessed for oxyhemoglobin, deoxyhemoglobin, and oxygen saturation (HbO, HbR, and SO2, respectively). The fNIRS data were analyzed and correlated with improvement in neuropsychology scores at 1-month follow-up. There was a significant reduction in HbO in the patient group, while it increased in controls (-2.57E-05 vs. 1.09E-04 mM, p < 0.001). The reduced HbO significantly improved after embolization (-2.1E-04 vs. 9.9E-04, p = 0.05, q = 0.05). In patients with aggressive DAVF (Cognard 2B and above), the change was highly significant (p < 0.001; q = 0.001). A moderate correlation was observed between MMSE scores and HbO changes (ρ = 0.4). fNIRS is a useful non-invasive modality for the assessment of DAVF, and could potentially assist in bedside monitoring of treatment response.

The Predictability of Echocardiography in Children with Primary Pulmonary Hypertension and Its Comparison with Cardiac Catheterization Parameters

Background: Pulmonary hypertension (PH) is a serious problem with high mortality in children, so early diagnosis of this condition is critical. Echocardiography is a non-invasive hemodynamic assessment tool, which facilitates serial follow-ups for hypertensive patients. Objectives: The aim of this study was to evaluate the importance of echocardiographic parameters in children with PH and their correlation with cardiac catheterization parameters. Methods: This cross-sectional study was performed on the records of 20 children with primary PH referred to the pediatric Cardiology Department and clinic of Imam Reza Hospital, Mashhad, Iran, during 2001-2016. The correlation between echocardiography and cardiac catheterization findings was assessed to determine the predictability of echocardiographic parameters in primary pulmonary hypertension. Results: Based on the findings, the mean values of tricuspid regurgitation pressure gradient (TRPG) and peak early diastolic transpulmonary valve pressure gradient (PRPG) were 76.33 ± 22.8 and13.18 ± 44.2 mmHg, respectively. The mean of RA systolic pressure, RA diastolic pressure, RA mean pressure were 13.62 ± 4.43, 5.12 ± 2.1, and 6.77 ± 4.08, respectively. The analysis of data showed a significant correlation between systolic pulmonary artery pressure (PAP) and TRPG (r = 0.62; P = 0.008). We found no significant correlation between systolic PAP and PRPG (r = 0.58; P = 0.03). Additionally, diastolic PAP significantly correlated with TRPG (r = 0.67; P = 0.003) and PRPG (r = 0.64; P = 0.04). Moreover, a significant correlation was observed between mean PAP and TRPG (r = 0.66; P = 0.004) and PRPG (r = 0.64; P = 0.04). Conclusions: Echocardiographic approach is a safe and sensitive method for diagnosis of primary pulmonary hypertension. We found a strong correlation between mean PAP and two variables of TRPG and PRPG.

The role of serial right heart catheterization in risk stratification and management of pulmonary arterial hypertension

Introduction Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial blood pressure secondary to increased pulmonary vascular resistance. Despite the advances in medical therapy, PAH continues to be a significant cause of morbidity and mortality. Areas covered Invasive hemodynamic assessment by performing a right heart catheterization (RHC) remains the gold standard to confirm the diagnosis and further management of PAH. The RHC also helps to determine the severity of RV dysfunction and can be used to test for pulmonary vasoreactivity. After diagnosis and initiation of therapy, many PAH centers continue to perform RHC at regular intervals to monitor for disease progression and alter management. In this review, we discuss the importance of risk stratification in PAH, the role of RHC in the evaluation and treatment of these patients and compare non-invasive risk assessment tools to that of RHC. Expert opinion RHC is useful for diagnosis of PAH, assessing the risk of mortality and morbidity, directing the escalation and de-escalation of therapy, and monitoring for disease progression. In the current era of improved non-invasive cardiac hemodynamic assessment, the role for routine follow-up serial RHC in patients with PAH needs to be reassessed in future studies. With the availability of non-invasive risk assessment tools such as REVEAL Lite 2, it may be reasonable to reconsider the role of annual or protocoled RHC, and instead, move to an “as needed” and individual basis.

Non-invasive Maternal Hemodynamic Assessment to Classify High-Risk Pregnancies Complicated by Fetal Growth Restriction.

To verify whether the use of the temporal criterion of 32 weeks' gestation is effective in identifying maternal hemodynamic differences between early- and late-onset fetal growth restriction (FGR), and to test the statistical performance of a classificatory algorithm for FGR. A prospective multicenter study conducted at three centers over 17 months. Singleton pregnant women with a diagnosis of FGR based on the international Delphi survey consensus at ≥ 20 weeks of gestation were included. FGR was classified as early-onset if diagnosed <32 weeks' gestation and as late-onset if ≥32 weeks. Hemodynamic assessment was performed by USCOM-1A at the time of FGR diagnosis. Comparisons between early- and late-onset FGR among the entire study cohort, FGR associated with hypertensive disorders of pregnancy (HDP-FGR), and isolated FGR (i-FGR) were performed. In addition, HDP-FGR cases were compared to i-FGR, regardless of the temporal cut-off of 32 weeks' gestation. Finally, a classificatory analysis based on the Random Forest model was performed to identify significant variables with the ability to differentiate FGR phenotypes. During the study period, 146 pregnant women fulfilled the inclusion criteria. In 44 cases, FGR was not confirmed at birth, thus limiting the final study population to 102 patients. In 49 (48.1%) women, FGR was associated to HDP. Fifty-nine (57.8%) cases were classified as early-onset. Comparison of the maternal hemodynamics between early- and late-onset FGR did not show any difference. Similarly, non-significant findings were observed in sensitivity analyses performed for HDP-FGR and for i-FGR. In turn, comparison between pregnant women with FGR and hypertension and women with i-FGR, independently of the gestational age at FGR diagnosis, revealed substantial differences, with the former showing higher vascular peripheral resistances and lower cardiac output, among other significant parameters. The classificatory analysis identified both phenotypic and hemodynamic variables as relevant in distinguishing HDP-FGR from i-FGR (p=0.009). Our data show that HDP, rather than gestational age at FGR diagnosis, allows to appreciate specific maternal hemodynamic patterns and to accurately distinguish two different FGR phenotypes. In addition, maternal hemodynamics, alongside phenotypic characteristics, play a central role in classifying these high-risk pregnancies.

Sex differences in cortical‐hypothalamic circuitry mediating cardiovascular disease risk

Endocrine and autonomic stress responses adapt the body to real or perceived threats by engaging physiological pathways to maintain homeostasis. Unfortunately, the burden of prolonged stress contributes to maladaptive stress responding, increasing risk for pathologies including cardiometabolic disorders. However, the circuit mechanisms integrating endocrine and autonomic stress responses have yet to be defined. Our previous studies found that glutamate neurons of the infralimbic cortex (IL) have sex‐specific effects on endocrine and cardiovascular stress reactivity. While the IL is important for coordinating behavioral and physiological responses to stress, these cortical cells do not directly innervate the secretory or pre‐autonomic cells that initiate endocrine and autonomic stress responses. However, we previously found that the posterior hypothalamus (PH) receives dense stress‐activated inputs from the IL. Thus, the current study tests the hypothesis that IL glutamate release in the PH mediates sex‐specific effects on stress integration. To test this hypothesis, adult male and female Sprague‐Dawley rats received stereotaxic injections in the IL of a viral‐packaged construct expressing channelrhodopsin‐2 and bilateral fiber optics targeting the PH to stimulate IL synapses in the PH. After recovery and acclimatization to handling, rats were tested in the real‐time place preference paradigm to examine behavioral preference or aversion for circuit stimulation. These data indicate that IL‐PH signaling is preferred by males and that females have neither preference nor aversion for IL‐PH stimulation. Additionally, acute restraint was used to examine glucose and corticosterone responses to stress. Results found that IL synapses in the PH decrease stress‐induced glucose mobilization without affecting corticosterone in male rats. In contrast, IL‐PH stimulation in females increases corticosterone responses to restraint but does not affect glucose mobilization. Furthermore, non‐invasive assessment of hemodynamics indicate that IL‐PH stimulation increases heart rate in females but not males. Thus, the IL‐PH circuit increases place preference and reduces glucose responses to stress in males, while increasing corticosterone stress responses and heart rate in females. Taken together, these data suggest that the PH represents a key node for sex‐specific integration of descending cortical signals with endocrine and autonomic stress reactivity. Ultimately, sex‐specific delineation of stress‐regulatory neurocircuitry may provide insight into the differential impact of stress pathologies in men and women.

Clinical and Prognostic Role of Noninvasive Hemodynamic Assessment in Left Ventricular Assist Device Carriers.

Persistence of heart failure symptoms or suboptimal hemodynamic is a frequent condition in LVAD carriers, associated with adverse outcome. Invasive hemodynamic optimization was associated with a better outcome. Our group recently validated an echocardiographic protocol to noninvasively assess hemodynamics of LVAD patients. Aim of this prospective study was to investigate its utility in clinical practice and its prognostic role. From February 2016 to February 2019 fifty-five LVAD carriers (HVAD/HM3 34/21; age 61 ± 10 years, 89% males; INTERMACS profile at LVAD implantation ≤3 68%). A two-phased protocol was performed. First, the patient underwent clinical evaluation. Second, an echo-Doppler blinded to clinical data was performed. Clinical and echo-Doppler evaluation both identified patients with "optimal hemodynamic profile" (normal left and right estimated atrial pressures) versus other profiles. clinical evaluation overestimated the presence of an optimal profile compared with echo-Doppler (83% vs. 59%). The presence of overt heart failure identified patients with the highest risk of adverse outcomes (death or hospitalization for HF at 6 months: HR 15, 95% CI, 5.5-39, P < 0.001). An optimal profile by echo-Doppler was associated with a better outcome among patients without overt heart failure (death or hospitalization for HF at 6 months: HR 0.08, 95% CI, 0.01.5-0.64, P < 0.02). After echo-Doppler, the clinician modified treatment in 46 cases (37%). Noninvasive evaluation of hemodynamics by echo-Doppler adds significant prognostic information in LVAD patients without overt HF and is a valuable tool to tailor treatment in the outpatient follow-up of LVAD carriers. Visual abstract: http://links.lww.com/ASAIO/A783.