Aortic Characteristic Impedance Research Articles

Dapagliflozin Enhances Arterial and Venous Compliance During Exercise in Heart Failure With Preserved Ejection Fraction: Insights From the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial.

Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. In this secondary analysis from the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial, 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters.

Blood pressure or flow measurements have been associated withvascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters.

Blood pressure or flow measurements have been associated withvascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

Effects of aerobic exercise training on cerebral pulsatile hemodynamics in middle-aged adults with elevated blood pressure/stage 1 hypertension.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o2peak) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o2peak increased 6% in AET and decreased 4% in CON (P < 0.05). Proximal aortic compliance increased (P = 0.04, partial η2 = 0.14) and aortic characteristic impedance decreased (P = 0.02, partial η2 = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant (P = 0.07, partial η2 = 0.11) compared with CON. Working memory reaction time improved with AET but not CON (P = 0.02, partial η2 = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics.NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

Aortic Characteristic Impedance and Suspected Mild Cognitive Impairment in a Community-Based Healthy Population.

Aging of the proximal aorta can lead to increased pressure and flow pulsatility in the cerebral microcirculation, which may cause cognitive impairment. This study investigated the association between aortic characteristic impedance (Zc), an indicator of regional stiffness of the proximal aorta, and suspected mild cognitive impairment (MCI), compared with carotid-femoral pulse wave velocity (CFPWV). A total of 1461 healthy community residents (46.4% men; age range, 35-96 years [mean±SD, 59.9±11.8 years]) without a history of cardiovascular events or stroke were included in the study. Zc was estimated using applanation tonometry and echocardiography. Cognitive function was assessed using the Mini-Mental State Examination. Education-adjusted cut points were used to define suspected MCI. Subjects with suspected MCI (n=493 [33.7%]) had significantly higher Zc and CFPWV than those without. In multivariable analysis, both Zc and CFPWV were inversely associated with Mini-Mental State Examination score. Zc (odds ratio per 1 SD, 1.22 [95% CI, 1.09-1.37] and CFPWV (odds ratio per 1 SD, 1.18 [95% CI, 1.01-1.38]) was also significantly associated with suspected MCI, after adjusting for age, sex, education level, mean arterial pressure, hypertension, diabetes, low-density lipoprotein cholesterol, and smoking status. In joint analysis, Zc was significantly associated with suspected MCI, but CFPWV was not. In the age subgroups of <50 years and 50 to 70 years, only Zc was significantly associated with suspected MCI. This study found that Zc was significantly associated with Mini-Mental State Examination score and suspected MCI, especially in younger and middle-aged adults. These findings suggest that Zc may be a useful biomarker for identifying individuals at risk for MCI.

Measures of aortic function independently predict adverse events in females with thoracic aortic aneurysms

Abstract Background/Introduction Thoracic aortic aneurysm (TAA) is a disease associated with high morbidity and mortality. TAA is more common in males, but females with TAA experience faster aneurysm growth and a higher risk of acute aortic syndromes and death. We have previously demonstrated that measures of aortic function, correlating with abnormal aortic wall architecture and reflecting worse aortic health, are independently associated with aneurysm size and expansion, specifically among females. To date, international guidelines focus on aneurysm size to determine timing for prophylactic surgical intervention, however adverse outcomes can occur before surgical thresholds are met, highlighting the need for novel risk assessment tools in TAA. Purpose We sought to evaluate whether measures reflecting proximal aortic function (where the TAA is located) would independently predict adverse outcomes in men and women with TAA. These measures include: aortic characteristic impedance (Zc), proximal aortic compliance (PAC), proximal aortic pulse wave velocity (PAoPWV) and the aortic stiffness-thickness product (Eh). Study summary is illustrated in Picture 1. Methods We performed a prospective study of 102 males and 48 females with TAA. Measures reflecting proximal aortic function were non-invasively assessed with validated methodology combining arterial tonometry with transthoracic echocardiography at the time of enrollment. The primary outcome was a composite of acute aortic syndromes, death, or guideline-directed aortic surgery. We used Cox proportional hazard models to determine the independent associations of aortic function measures with the primary outcome. PAoPWV and Eh were log-transformed to reduce skewness. Models were adjusted for variables previously demonstrated to predict adverse outcomes in TAA: age, sex, aneurysm size and etiology, and mean arterial pressure (MAP). Sex-specific models were performed if the interaction of sex *aortic function measure was significant (P≤0.05). Results Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and MAP was 90±10 mmHg (not different between and women, P&amp;gt;0.07 for each). Mean follow up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. Our primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 8 deaths). Interaction terms of sex with each of the aortic function variables were significant (P&amp;lt;0.04 for each). Results of the sex-specific models are summarized in Picture 2. We observed that higher Zc, PAoPWV and Eh, and lower PAC were each independently associated with an increased risk of adverse outcomes among females only. Conclusions Among females with TAA, measures of proximal aortic function are independent predictors of adverse events, highlighting novel markers for risk stratification and therapeutic targeting.Illustrative Summary

Assessment of Aortic Characteristic Impedance and Arterial Compliance from Non-invasive Carotid Pressure Waveform in The Framingham Heart Study

The primary goal of this study was to test the hypothesis that a hybrid intrinsic frequency-machine learning (IF-ML) approach can accurately evaluate total arterial compliance (TAC) and aortic characteristic impedance (Zao) from a single noninvasive carotid pressure waveform in both women and men with heart failure (HF). TAC and Zao are cardiovascular biomarkers with established clinical significance. TAC is lower and Zao is higher in women than in men, so women are more susceptible to the consequent deleterious effects of them. Although the principles of TAC and Zao are pertinent to a multitude of cardiovascular diseases, including HF, their routine clinical use is limited because of the requirement for simultaneous measurements of flow and pressure waveforms. For this study, the data were obtained from the Framingham Heart Study (n=6,201, 53% women). The reference values of Zao and TAC were computed from carotid pressure and aortic flow waveforms. IF parameters of carotid pressure waveform were used in ML models. IF models were developed on n=5,168 of randomly selected data and blindly tested the remaining data (n=1,033). The final models were evaluated in patients with HF. Correlations between IF-ML and reference values in all HF and HF with preserved ejection fraction for TAC were 0.88 and 0.90, and for Zao were 0.82 and 0.80, respectively. The classification accuracy in all HF and HF with preserved ejection fraction for TAC were 0.9 and 0.93, and for Zao were 0.81 and 0.89, respectively. In conclusion, the IF-ML method provides an accurate estimation of TAC and Zao in all subjects with HF and in the general population.

Longitudinal Hemodynamic Correlates of and Sex Differences in the Evolution of Blood Pressure Across the Adult Lifespan: The Framingham Heart Study.

Background Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle-aged and older adults. Relative contributions of aortic stiffness and premature wave reflection to increases in pulse pressure remain controversial. Methods and Results We evaluated visit-specific values and change in key correlates of pulse pressure, aortic characteristic impedance, forward and backward wave amplitude, and global reflection coefficient, at 3 sequential examinations of the Framingham Generation 3 (N=4082), Omni-2 (N=410), and New Offspring Spouse (N=103) cohorts (53% women). Data were analyzed using repeated-measures linear mixed models adjusted for age, sex, and risk factor exposures. Pulse pressure increased markedly with age after midlife (age and age-squared terms, P<0.0001), particularly in women (age slope 3.1±0.2 mm Hg/decade higher in women, P<0.0001). In sex-specific models, change in pulse pressure was closely related (all P<0.0001) to baseline (6.7±0.2 and 7.3±0.2 mm Hg/SD in men and women, respectively) and change (11.8±0.1 and 11.7±0.1 mm Hg/SD) in forward wave amplitude, whereas relations with baseline (2.1±0.15 and 2.0±0.14 mm Hg/SD) and change (4.0±0.13 and 3.4±0.11 mm Hg/SD) in global reflection coefficient were weaker. Global reflection coefficient fell as aortic characteristic impedance increased (P<0.0001), consistent with the hypothesis that impedance matching reduces relative wave reflection in the arterial system. Conclusions Proximal aortic stiffening, as assessed by higher aortic characteristic impedance and larger forward wave amplitude, is strongly associated with longitudinal increase in pulse pressure, especially in women, whereas wave reflection has more modest relations.

MARKED INCREASES IN PROXIMAL AORTIC CHARACTERISTIC IMPEDANCE AND HENCE FORWARD WAVE PRESSURES BEYOND BRACHIAL BLOOD PRESSURE IN ANGIOGRAPHIC PROVEN CORONARY ARTERY DISEASE

Objective: Although indexes of aortic stiffness increase the risk for coronary artery disease (CAD), the extent to which proximal aortic stiffness increases enhance central arterial forward wave pressures beyond changes in peripheral pressures, is uncertain. We aimed to determine whether increases in proximal aortic stiffness, as indexed by aortic characteristic impedance (Zc) translate into an enhanced central arterial pressure for a given brachial BP. Design and method: From central pressure, aortic velocity and outflow tract diameter measurements and echocardiography, we determined Zc and arterial pressure wave morphology in 71 patients with angiographic proven CAD and all other cardiac pathology excluded. We compared central arterial function in these patients with 230 age and sex-matched controls from a community study, and in patients with stroke and CLI (n = 287) diagnosed in a hospital setting. Results: Adjusting for confounders, including mean arterial pressure, and aortic root diameter, as compared to controls, both Zc and the pressures generated by the product of peak aortic flow (Q) and Zc (PQxZc) were markedly increased in patients with CAD (p&lt;0.0001) and those with stroke or CLI (p&lt;0.005). Moreover, compared to patients with stroke and CLI, those with CAD also had marked increases in both Zc and PQxZc (p&lt;0.0001). Consequently, with adjustments for the same confounders, pressures generated by forward wave pressures (Pf) were markedly increased in patients with CAD as compared to controls and to patients with alternative arterial diseases (p&lt;0.0001). Importantly, after further adjustments for brachial PP or SBP, the higher Pf values in patients with CAD were retained (p&lt;0.005 to &lt;0.0001). However, with adjustments for brachial SBP and confounders, central aortic PP did not differ between groups. Conclusions: Independent of confounders and aortic root diameter, a marked increase in proximal aortic Zc occurs in patients with CAD as compared to both controls and patients with arterial disease in alternative beds. This translates into a greater central arterial pulsatile load determined by forward travelling pressure waves, but not peak central PP than that predicted by brachial BP measurements. These data support a need for intense brachial BP lowering in CAD.

Novel Measures of Arterial Hemodynamics and Wave Reflections Associated With Clinical Outcomes in Patients With Heart Failure.

Background Arterial stiffness and earlier wave reflections can increase afterload and impair cardiovascular function. Most prior studies have been performed in patients with preserved left ventricular function. We describe novel measures of pulsatile arterial hemodynamics and their association with clinical outcomes in patients with heart failure with reduced ejection fraction. Methods and Results Participants with heart failure with reduced ejection fraction (n=137, median age 56 years, 49% women, 58% Black) and age-matched healthy controls (n=124) underwent measurements of large artery stiffness and pulsatile arterial hemodynamics. Carotid-femoral pulse wave velocity and augmentation index were assessed using radial applanation tonometry. Pressure-flow analyses derived reflected wave transit time, the systolic pressure-time integral imposed by proximal aortic characteristic impedance, and the pressure-time integral from wave reflection (wasted pressure effort). Cox proportional hazards models defined associations between hemodynamic measures and (1) all-cause death and (2) a combined end point of left ventricular assist device implant, heart transplant, and death, at 2 years adjusted for race, BNP (B-type natriuretic peptide), and the Meta-Analysis Global Group in Chronic Heart Failure Risk Score. Compared with controls, participants with heart failure with reduced ejection fraction exhibited similar carotid-femoral pulse wave velocity (6.8±1.6 versus 7.0±1.6 m/s, P=0.40) but higher augmentation index normalized to a heart rate of 75 bpm (13±2% versus 22±2%, P<0.001). Shorter reflected wave transit time (ie, earlier wave reflection arrival to the proximal aorta) was associated with an increased risk of death (adjusted hazard ratio [aHR] 1.67 [95% CI 1.03-1.63]) and the combined end point of death/left ventricular assist device/heart transplant (aHR, 1.61 [95% CI, 1.06-2.44]) at 2 years. Wasted pressure effort/proximal aortic characteristic impedance, representing the proportion of systolic load from wave reflection versus aortic root characteristic impedance, was univariately associated with death (hazard ratio (HR), 1.44 [95% CI, 1.05-1.97]) and with death/left ventricular assist device/heart transplant on univariate (HR, 1.42 [95% CI, 1.07-1.88]) and multivariable (aHR, 1.40 [95% CI, 1.02-1.93]) analysis. Conclusions Increased left ventricular systolic load from premature wave reflections is associated with adverse clinical outcomes in patients with heart failure with reduced ejection fraction.

Aortic Biomechanics: Comment.

We read with interest the recent review of aortic biomechanics and their clinical applications by Gregory et al.1 The authors should be congratulated for addressing this important but often underappreciated subject. Nevertheless, we are obligated to mention that the authors did not acknowledge or discuss a series of pertinent studies conducted in chronically instrumented dogs describing the effects of anesthetics on aortic biomechanics. This canine model is highly relevant to the review,1 because the cardiovascular effects of anesthetics are virtually identical in dogs and humans. We and others used aortic input impedance spectra in the frequency domain2 that were interpreted with a three-element Windkessel model of the arterial circulation, incorporating aortic mechanical properties,3 to quantify the effects of anesthetics on left ventricular afterload.4–13 We first demonstrated that isoflurane reduces total arterial resistance in a concentration-dependent manner and modestly increases total arterial compliance (primarily determined by the aorta and proximal great vessels14), but does not affect characteristic aortic impedance (the resistance of the aorta itself).4 In contrast, the potent vasodilator sodium nitroprusside decreased total arterial resistance and markedly increased total arterial compliance when the drug was administered at infusion rates that resulted in levels of hypotension equivalent to those observed during the administration of isoflurane. The findings with sodium nitroprusside confirmed previous observations in dogs15 and humans.16,17 Taken together, these data indicated that the primary effect of isoflurane on the determinants of left ventricular afterload was related to its well-known actions on arteriolar resistance vessels and not on the aorta itself, whereas sodium nitroprusside altered left ventricular afterload through its effects on both arteriolar vasomotor tone and the mechanical properties of the aorta. Similar findings with isoflurane were also reported in an acutely instrumented open-chest swine model.13 We further showed that desflurane also reduces total arterial resistance but does not substantially affect total arterial compliance and characteristic aortic impedance, actions that were indistinguishable from those of isoflurane.6 However, sevoflurane did not affect total arterial resistance but caused small increases in total arterial compliance and characteristic aortic impedance,6 observations that mirrored those seen with the obsolete volatile anesthetic halothane.4Isoflurane increased aortic distensibility (concomitant with reductions in aortic pressure) and did not affect characteristic aortic impedance when these parameters were calculated using simultaneous measurements of aortic diameter, pressure, and blood flow.5 These findings reinforced the conclusion that alterations in the aortic mechanical properties are not responsible for the actions of isoflurane on left ventricular afterload. In contrast to the findings with isoflurane in dogs with normal left ventricular function, this volatile anesthetic did not exert beneficial changes in total arterial resistance, characteristic aortic impedance, and total arterial compliance in a canine model of heart failure with reduced ejection fraction induced by chronic rapid ventricular pacing.7 We conducted additional investigations in normal and cardiomyopathic dogs with the anesthetic noble gas xenon,8 and with the intravenous anesthetics propofol,9,10 etomidate,11 and dexmedetomidine12 that revealed unique insights into the actions of these medications on the contributions of altered aortic mechanics to left ventricular afterload in vivo. These studies document that the impact of anesthetics on aortic biomechanics has been examined previously in clinically relevant animal models, contrary to the article’s assertion.1The authors declare no competing interests.

Aortic Biomechanics: Reply.

We thank the authors for their thoughtful letter and informative review regarding the effects of anesthesia on the cardiovascular system.1 This previous work using animal models has been foundational in framing our understanding of arterial physiology and the effects of anesthetic agents. Our omission of these previous works in our recently published review on aortic biomechanics was not meant to diminish their importance.2 Rather, the purpose of our review was to focus on concepts related to the material properties of the aorta itself in health, disease, surgery, and anesthesia, and to propose that local aortic changes may have both physiologic and clinical ramifications through the aorta’s relationship with the heart and distal arteries.Certainly, the previous studies highlighted by Dr. Pagel et al., using a three-element Windkessel model in animals, have provided important details on the effects of anesthesia on aortic biomechanics. But we respectfully submit that it may not tell the whole story. First, compliance, as calculated in the Windkessel model, is total arterial compliance, not exclusively aortic.3 The contribution of small arteries to compliance is considerable and, in humans, increases with age-related aortic stiffening, thereby “blurring the distinction between large and small artery function.”4 As such, the described changes to compliance from the Windkessel model likely cannot be attributed to the aortic biomechanical properties alone. Second, we disagree with the contention that characteristic aortic impedance is “the resistance of the aorta itself.” Although aortic impedance has the units of resistance, it exists only with pulsatile flow and pressure and is a function of the modulus of elasticity and radius.3 Similar to compliance, there is no exact anatomical aortic correlate to aortic impedance, although it characterizes the vessel in close proximity to the measurement. Therefore, although we agree that left ventricular afterload can be modeled using the Windkessel, we believe that aortic biomechanics as defined by the authors is only partly responsible.Aortic biomechanics, at the level of local aortic microstructure and mechanical behavior, has until now been limited to bench-top testing on excised tissue. With recent advancements in imaging technology, there are new opportunities to explore the aorta in vivo and hopefully gain new insights into local aortic biomechanical properties in the clinical anesthesia environment. As we assert in our review, this work has yet to be done.Our understanding of cardiovascular physiology has greatly benefitted from the previous scientific work of Dr. Pagel and others who have published using similar arterial system models. They have put together much of the puzzle as it pertains to anesthesia and cardiovascular physiology. We believe that the additional perspectives on aortic biomechanics described in our review hold potential to add a piece to said puzzle, not replace it altogether.The authors declare no competing interests.

Pulsatile energy consumption as a surrogate marker for vascular afterload improves with time post transcatheter aortic valve replacement in patients with aortic stenosis.

The effect of arterial stiffening on elevated pulsatile left ventricular afterload patients with aortic stenosis (AS) is pronounced beyond systemic hypertension. Circulatory afterload pulsatile efficiency (CAPE) is a marker of vascular function, defined as the ratio of steady state energy consumption (SEC) to maintain systemic circulation and pulsatile energy consumption (PEC). Twenty patients aged 80 ± 7 years were assessed at baseline and a median of 60 days post transcatheter aortic valve replacement (TAVR), with pulsatile vascular load calculated using simultaneous radial applanation tonometry derived aortic pressure and cardiac magnetic resonance phase-contrast imaging derived ascending aortic flow. Eight out of 20 patients had a reduction in PEC post TAVR, and the reduction of PEC correlated strongly with the number of days post TAVR (R = 0.62, P < 0.01). Patients assessed within the 100 days of TAVR had a rise in their PEC when compared to baseline (0.19 ± 0.09 vs 0.14 ± 0.08 W, P = 0.04). Baseline PEC correlated moderately with baseline SEC (R = 0.49, P = 0.03), and a high baseline PEC was predictive of post TAVR PEC reduction (R = 0.54, P =0.01). Overall, no significant differences were found between baseline and post TAVR for systolic aortic pressure (131 ± 20 vs 131 ± 20 mmHg), systemic vascular resistance (1894 ± 493 vs 2015 ± 519 dynes.s/cm5), aortic valve ejection time (337 ± 22 vs 324 ± 34 ms) or aortic characteristic impedance (120 ± 48 vs 107 ± 41 dynes.s/cm5). Improved flow profiles after TAVR likely unmask the true vascular properties by altering ventriculo-valvulo-arterial coupling, leading to downstream vascular remodelling secondary to flow conditioning, and results in eventual improvement of pulsatile afterload as reflected by our proposed index of CAPE.

Abstract 11892: Novel Measures of Arterial Stiffness and Wave Reflections Associate With Clinical Outcomes in Patients With Heart Failure

Introduction: Arterial stiffness and earlier wave reflections can increase afterload and impair cardiovascular function. Most prior studies have been performed in patients with preserved left ventricular (LV) function. Hypothesis: Novel measures of pulsatile arterial hemodynamics are predictive of worse clinical outcomes in patients with HFrEF. Methods: Patients with HFrEF (N=137, median age 56, 49% female, 58% Black) and age-matched healthy controls (N=124) underwent measurements of large artery stiffness and pulsatile arterial hemodynamics from 2015-2019 at a single study visit. Carotid-femoral pulse wave velocity (CF-PWV) and augmentation index (AIx) were assessed using high-fidelity applanation tonometry. In HFrEF patients, pressure-flow analyses were performed to derive aortic characteristic impedance (QZc), reflected wave transit time (RWTT), and wasted pressure effort (WPE). In HFrEF patients, Cox proportional hazards models examined associations between vascular function measures and 1) all-cause death and 2) a combined endpoint of left ventricular assist device (LVAD) implant, heart transplant (HT), and death at 2 years adjusted for race, BNP, and MAGGIC risk score. Results: Compared to controls, patients with HFrEF had similar CF-PWV (6.8+/-1.6 v. 7.0+/-1.6 m/s, P=0.4), and higher AIx normalized to a HR of 75 bpm (13+/-2% v. 22+/-2%, P&lt;0.001). Among HFrEF patients, a shorter RWTT was associated with death (adjusted hazard ratio [aHR] 0.60, 95% confidence interval [CI] 0.37-0.97) and the combined endpoint of death/LVAD/HT (aHR 0.62, 95% CI 0.41-0.94) at 2 years ( Figure ). WPE/QZc, which represents the proportion of systolic load from wave reflection, was associated with the combined endpoint on multivariable analysis (aHR 1.40, 95% CI 1.02-1.93). AIx and PWV were not predictive of clinical outcomes. Conclusion: Increased LV systolic load from premature wave reflections is associated with adverse clinical outcomes in patients with HFrEF.

Attenuated Relationships Between Indexes of Volume Overload and Atrial Natriuretic Peptide in Uncontrolled, Sustained Volume-Dependent Primary Hypertension.

Whether systolic blood pressure (SBP) control in sustained volume-dependent primary hypertension is associated with blunted ANP (atrial natriuretic peptide) relationships with indexes of volume load is unknown. Systemic hemodynamics (central pressure, echocardiographic aortic velocity and diameter measurements in the outflow tract), circulating ANP concentrations (ELISA assays) and glomerular and tubular function (24-hour urine collections [n=519]) were determined in a community of African ancestry (n=772). As compared with those with a controlled SBP, those with an uncontrolled SBP (n=198) showed lower ANP concentrations (P<0.005) despite higher stroke volume and cardiac output (P<0.0001) and renal differences consistent with enhanced fluid retention. In those with a controlled SBP, fractional Na+ excretion (FeNa+; P<0.0005) and creatinine clearance (glomerular filtration rate; P<0.005) were inversely associated with ANP concentrations independent of confounders. Moreover, in those with a controlled SBP, stroke volume and cardiac output (P<0.0001) were independently and positively associated with ANP concentrations. In addition, in those with a controlled SBP, ANP concentrations were independently and inversely associated with systemic vascular resistance (SVR; P<0.0001) and aortic characteristic impedance (Zc; P<0.005). By contrast, in those with uncontrolled SBP, no relationships between either stroke volume (P>0.25), cardiac output (P>0.29), FeNa+ (P>0.77), or glomerular filtration rate (P>0.47) and ANP concentrations were noted. Furthermore, in those with an uncontrolled SBP, no relationships between ANP concentrations and SVR or Zc were observed (P>0.34). In a population where primary hypertension is strongly volume-dependent, those with an uncontrolled SBP have an attenuated relationship between ANP and both renal and hemodynamic indexes of volume overload and the vascular effects of ANP.

Proximal aortic stiffness modifies the relationship between heart rate and backward wave and hence central arterial pulse pressure.

A lower heart rate (HR) increases central blood pressure through enhanced backward wave pressures (Pb). We aimed to determine whether these relationships are modified by increases in aortic stiffness. Using non-invasive central pressure, aortic velocity and diameter measurements in the outflow tract (echocardiography), we assessed the impact of aortic stiffness on relationships between HR and arterial wave morphology in 603 community participants < 60 years of age, 221 ≥ 60 years, and in 287 participants with arterial events [stroke and critical limb ischemia (CLI)]. As compared to community participants < 60 years, those ≥ 60 years or with events had increased multivariate adjusted proximal aortic characteristic impedance (Zc) and carotid femoral pulse wave velocity (PWV) (p < 0.05 to < 0.0001). Community participants ≥ 60 years and those with events also had a greater slope of the inverse relationship between HR and Pb (p < 0.001 for comparison). While in community participants < 60 years, no interaction between indexes of aortic stiffness and HR occurred, in those ≥ 60 years (p < 0.02) and in those with arterial events (p = 0.001), beyond aortic root diameter, an interaction between Zc and HR, but not between PWV and HR independently associated with Pb. This translated into stepwise increases in the slope of HR-Pb relationships at incremental tertiles of Zc. Although HR was inversely associated with the systemic reflection coefficient in community participants ≥ 60 years (p < 0.0001), adjustments for the reflection coefficient failed to modify HR-Pb relations. Beyond the impact on systemic wave reflection, increases in proximal aortic stiffness enhance the adverse effects of HR on Pb and hence central BP.

SEX DIFFERENCES IN ARTERIAL HEMODYNAMICS IN PATIENTS WITH DEGENERATIVE THORACIC AORTIC ANEURYSMS

BackgroundWomen with thoracic aortic aneurysms (TAA) experience worse outcomes at smaller aortic sizes when compared to men. Further, we have previously shown that female sex is associated with faster aneurysm growth, which is unique to individuals affected with degenerative forms of TAA (dTAA). Therefore, we sought to evaluate the potential differences in arterial health parameters (arterial stiffness and hemodynamics) that could explain this sex-specific difference in dTAA growth and outcomes.Methods and ResultsIn a subgroup of individuals with dTAA from a previously published prospective cohort study, we compared aortic stiffness and hemodynamics between sexes. We included 80 participants (33% women) with unoperated dTAA. Aortic stiffness, central blood pressure, and measures of steady and pulsatile arterial load were estimated with validated techniques that combine applanation tonometry with transthoracic echocardiography. Comparison of baseline characteristics between males and females is presented in the Table. Univariable linear regression analyses showed that women had higher aortic characteristic impedance (mean difference [MD]= 37.35 ± 16.07 dyne x s/cm-5, P=0.03) and reflected pressure wave amplitude (MD= 4.34 ± 2.05 mmHg, P=0.04), and lower total arterial compliance (MD= -0.65 ± 0.18 mL/mmHg, P=0.001) than men. In multivariable linear regression analyses (adjusted for age, body-mass index, hypertension, mean arterial pressure, diabetes, and smoking history), aortic characteristic impedance and reflected pressure wave amplitude remained significantly higher (respectively MD= 17.18 ± 6.36 dyne x s/cm-5, P=0.009, and MD= 1.74 ± 0.77 mmHg, P=0.03), while total arterial compliance (MD= -0.29 ± 0.09 mL/mmHg, P=0.002) was significantly lower in women compared to men. (Figure)ConclusionView Large Image Figure ViewerDownload Hi-res image Download (PPT) BackgroundWomen with thoracic aortic aneurysms (TAA) experience worse outcomes at smaller aortic sizes when compared to men. Further, we have previously shown that female sex is associated with faster aneurysm growth, which is unique to individuals affected with degenerative forms of TAA (dTAA). Therefore, we sought to evaluate the potential differences in arterial health parameters (arterial stiffness and hemodynamics) that could explain this sex-specific difference in dTAA growth and outcomes. Women with thoracic aortic aneurysms (TAA) experience worse outcomes at smaller aortic sizes when compared to men. Further, we have previously shown that female sex is associated with faster aneurysm growth, which is unique to individuals affected with degenerative forms of TAA (dTAA). Therefore, we sought to evaluate the potential differences in arterial health parameters (arterial stiffness and hemodynamics) that could explain this sex-specific difference in dTAA growth and outcomes. Methods and ResultsIn a subgroup of individuals with dTAA from a previously published prospective cohort study, we compared aortic stiffness and hemodynamics between sexes. We included 80 participants (33% women) with unoperated dTAA. Aortic stiffness, central blood pressure, and measures of steady and pulsatile arterial load were estimated with validated techniques that combine applanation tonometry with transthoracic echocardiography. Comparison of baseline characteristics between males and females is presented in the Table. Univariable linear regression analyses showed that women had higher aortic characteristic impedance (mean difference [MD]= 37.35 ± 16.07 dyne x s/cm-5, P=0.03) and reflected pressure wave amplitude (MD= 4.34 ± 2.05 mmHg, P=0.04), and lower total arterial compliance (MD= -0.65 ± 0.18 mL/mmHg, P=0.001) than men. In multivariable linear regression analyses (adjusted for age, body-mass index, hypertension, mean arterial pressure, diabetes, and smoking history), aortic characteristic impedance and reflected pressure wave amplitude remained significantly higher (respectively MD= 17.18 ± 6.36 dyne x s/cm-5, P=0.009, and MD= 1.74 ± 0.77 mmHg, P=0.03), while total arterial compliance (MD= -0.29 ± 0.09 mL/mmHg, P=0.002) was significantly lower in women compared to men. (Figure) In a subgroup of individuals with dTAA from a previously published prospective cohort study, we compared aortic stiffness and hemodynamics between sexes. We included 80 participants (33% women) with unoperated dTAA. Aortic stiffness, central blood pressure, and measures of steady and pulsatile arterial load were estimated with validated techniques that combine applanation tonometry with transthoracic echocardiography. Comparison of baseline characteristics between males and females is presented in the Table. Univariable linear regression analyses showed that women had higher aortic characteristic impedance (mean difference [MD]= 37.35 ± 16.07 dyne x s/cm-5, P=0.03) and reflected pressure wave amplitude (MD= 4.34 ± 2.05 mmHg, P=0.04), and lower total arterial compliance (MD= -0.65 ± 0.18 mL/mmHg, P=0.001) than men. In multivariable linear regression analyses (adjusted for age, body-mass index, hypertension, mean arterial pressure, diabetes, and smoking history), aortic characteristic impedance and reflected pressure wave amplitude remained significantly higher (respectively MD= 17.18 ± 6.36 dyne x s/cm-5, P=0.009, and MD= 1.74 ± 0.77 mmHg, P=0.03), while total arterial compliance (MD= -0.29 ± 0.09 mL/mmHg, P=0.002) was significantly lower in women compared to men. (Figure) Conclusion

WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

Abstract 039: Hybrid Intrinsic Frequency Machine Learning Approach For Calculation Of Total Arterial Compliance And Aortic Characteristic Impedance From A Single Carotid Waveform In Heart Failure With Preserved Ejection Fraction

Introduction: Previous studies demonstrated that heat failure with preserved ejection fraction (HFpEF) is characterized by abnormal arterial function and left ventricle (LV)-arterial coupling. Aortic characteristic impedance (Zc) and total arterial compliance (TAC) are well-established biomarkers for quantification of the arterial function. However, the routine clinical use of these biomarkers requires both pressure and flow measurements. Intrinsic Frequency (IF) method is a novel system-based mathematical approach for the analysis of the cardiovascular dynamics that can predict HF events (Cooper et al. Hypertension, 2021 PMID: 33390053). We hypothesized that a hybrid IF-machine learning (ML) approach can compute TAC and Zc from a noninvasive carotid waveform. Method: We used data from the Framingham Heart Study (FHS) (n=6168). The reference values of Zc and TAC were computed from carotid pressure and aortic flow waveforms. IF parameters of carotid pressure waveform were used in a fully connected feed-forward neural network model. The model was trained/validated/tested on 80% of randomly selected data from all FHS data. The final model was tested on the remaining 20% of the data blinded to all stages of ML development. Result: In blind test set data, our IF-ML models showed correlations of r=0.89 and r=0.79 with the reference value of TAC and Zc, respectively (Fig 1). More importantly, the TAC and Zc from our IF-ML models showed strong correlations among HFpEF patients (r=0.9 and r=0.77 respectively) (Fig.1) Conclusion: Since IFs can be measured noninvasively (e.g. an iPhone), this method can be used to facilitate routine and noninvasive evaluation of TAC and Zc in HFpEF.

EXCESSIVE PULSATILE POWER IN CAROTID ARTERIES IS ASSOCIATED REDUCED COGNITIVE FUNCTION: PULSATILE AND STEADY STATE ARTERIAL HEMODYNAMICS IN TWO COMMUNITY-BASED COHORTS

Objective: Increased pressure and/or flow pulsatility in the carotid arteries have been adversely associated with cerebral structure and function. We postulated that increased power(product of pressure and flow) pulsatility is even harmful to the microcirculation of high-flow organs. We aimed to investigate the associations of carotid pressure, flow, and power pulsatility with cognitive function and pulsatile and steady state hemodynamics in proximal aorta and carotid arteries. Design and method: A total 1855 adult aged &gt; = 30 years old were recruited for measurements of echocardiography and carotid sonography. We obtained hemodynamic parameters including pressure, flows, and power at proximal aorta and both carotid arteries. Proximal aortic pressure was determined by the tonometry waveform measured at common carotid arteries, calibrated by mean and diastolic pressure of brachial pressure. Pulsatility indexes(PIs) of pressure, flow and power in the proximal aorta and carotid arteries were calculated as the pulsatile value divided by mean value. We modelled the aorta-carotid interface with a large parent vessel(proximal aorta) branching into small (carotid) and large(distal aorta) daughter vessels and calculated the reflection coefficient and transmitting coefficient from aortic and carotid characteristic impedances. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA) score. Results: The pulsatile component was 10.3%(105/996mW) and 4.2%(11/268mW) of total aortic and carotid power, respectively. PIs of aortic pressure(r = -0.048,p = 0.0417), aortic flow(r = 0.060,p = 0.0101), aortic power(r = -0.080,p = 0.006), carotid flow(r = -0.085,p = 0.003), and carotid power(r = -0.097,p &lt; 0.0001) were all significantly associated with cognitive function, independent of age, sex, and education. Carotid power PI was significantly better than other PIs in the association with cognitive function. In the multivariable model, MoCA score was positively and negatively associated with carotid mean power (beta = 0.005,p &lt; .0001) and carotid pulsatile power(beta = -0.048,p &lt; .0001), respectively. With increasing aortic characteristic impedance and transmitting coefficient, and decreasing reflection coefficient, there was a significantly increased transmitting aortic power into carotid arteries(all p value &lt; 0.0001). Conclusions: Among all ascending aorta and carotid hemodynamics, carotid power PI was the hemodynamic parameter with the best correlation with cognitive function. Increased proximal aortic stiffness, and increased transmission and decreased reflection of the aortic power at the aorta-carotid interface were closely associated with increased carotid pulsatile power.