Aortic Impedance Research Articles

Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men

The increase in cardiovascular risk associated with metabolic syndrome (MS) seems higher in women than in men. We examined hemodynamics during head-up tilt in 252 men and 250 women without atherosclerosis, diabetes, or antihypertensive medication, mean age 48 years, using whole-body impedance cardiography and radial pulse wave analysis. MS was defined according to Alberti et al. 2009. Men and women with MS presented with corresponding elevations of systolic and diastolic blood pressure (10-14%, p ≤ 0.001) versus controls. Supine pulse wave velocity (16–17%, p < 0.001) and systemic vascular resistance (7–9%, p ≤ 0.026), and upright cardiac output (6–11%, p ≤ 0.008) were higher in both MS groups than controls. Elevation of supine aortic characteristic impedance was higher in women than in men with MS (16% vs. 8%, p = 0.026), and in contrast to men, no upright impedance reduction was observed in women. When upright, women but not men with MS showed faster return of reflected pressure wave (p = 0.036), and smaller decrease in left cardiac work (p = 0.035) versus controls. The faster upright return of reflected pressure, lower upright decrease in left cardiac work, and higher elevation of aortic characteristic impedance may contribute to the greater increase in MS-related cardiovascular risk in women than in men.

An experimental model of veno-venous arterial extracorporeal membrane oxygenation.

Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump-driven circuit. We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings.

Effects of Sacubitril-valsartan Compared with Enalapril on Arterial Hemodynamics, Cardiac Remodeling, and Quality of Life in Patients with Heart Failure and Reduced Ejection Fraction

Background Compared to angiotensin-converting enzyme inhibition alone, angiotensin receptor-neprilysin inhibition reduces cardiovascular mortality and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF). The pathophysiologic mechanisms responsible for these clinical benefits remain unclear but may be related to effects on central hemodynamics and cardiac structure and function. We sought to determine whether treatment of HFrEF with sacubitril/valsartan improves central aortic stiffness, cardiac remodeling, biomarkers of wall stress and injury, and quality of life compared with enalapril. Methods EVALUATE-HF was a prospective, randomized, multicenter, double-blind, double-dummy clinical trial of patients aged 50 or older with chronic HF, NYHA I-III symptoms, and EF of 40% or less. Participants were randomized 1:1 to treatment with sacubitril/valsartan (target dose 97/103 mg twice daily) versus enalapril (target dose 10 mg twice daily) for 12 weeks followed by open-label sacubitril/valsartan for 12 weeks (Figure). The primary study outcome was between group difference in change from baseline to week 12 in aortic characteristic impedance (Zc). Other prespecified outcomes included change from baseline to week 12 in levels of cardiac biomarkers and echocardiographic measures of cardiac structure and function as well as change in health-related quality of life assessed by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Results Between August 17, 2016 and January 26, 2019 we randomized 464 participants at 85 sites in the United States, of whom 231 were randomly assigned to sacubitril/valsartan and 233 to enalapril. For the overall population, mean age was 67.3 +/- 9.1 years, mean EF was 34 +/- 10%, median NTproBNP was 584 [IQR 244, 1467], 109 (23.5%) were female, 115 (24.8%) were black, 313 (67.4%) reported NYHA Class 2, and 391 (84.3%) were previously treated with an ACEi or ARB. We will present the primary results of the EVALUATE-HF study as initially submitted to the 2019 European Society of Cardiology Scientific Sessions, including the effects of sacubitril/valsartan compared with enalapril on change from baseline in central aortic stiffness, cardiac biomarkers, cardiac structure and function. We will also present new data regarding the time course and magnitude of changes in quality of life in both treatment groups during study follow up as well as the relationship of these changes to changes in cardiac structure, function, and biomarkers. Conclusions EVALUATE-HF will provide important mechanistic insights into established clinical benefits of sacubitril/valsartan in HFrEF. We will present detailed quality of life outcomes for the first time at HFSA 2019.

P4348Early assessment of left ventricular function by layer-specific strain and its relationship to pulsatile arterial load in patients with coronary slow flow

Abstract Background Previous studies reported controversial Left ventricular (LV) function impairment and pathophysiology in patients with coronary slow flow (CSF). Greater arterial load has been shown to increase aortic impedance and endothelial shear stress, potentially affecting coronary anatomy and function. We investigated LV systolic function by a new layer-specific strain technology and assessed the association between pulsatile arterial load and contractility. Methods and results A total of 70 patients with CSF and 50 controls with normal coronary angiography were included in the study. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium and epicardium (GLS-endo, GLS-mid, GLS-epi and GCS-endo, GCS-mid, GCS-epi) by two-dimensional speckle tracking imaging (2D-STI). Pulsatile arterial load was estimated by indexed arterial compliance (ACI). Layer-specific GLS showed a decreasing gradient from the endocardium to the epicardium in both controls and CSF group. GLS-endo and GLS-mid in CSF group were significantly lower than the control group (all P&lt;0.05). Layer-specific longitudinal strain showed a good correlation with the number of affected coronary arteries (all P&lt;0.05) and the mean thrombolysis in myocardial infarction frame count (TFC) (all P&lt;0.05). ACI was lower in CSF patients (P=0.005) and ACI was correlated negatively with layer-specific GLS (all P&lt;0.05). Conclusion Layer-specific evaluation of the LV provides an understanding of the layer-specific properties of the LV wall and the possible process of the LV impairment in patients with CSF. Greater pulsatile arterial load, as manifested by a lower ACI, is coupled with worse LV longitudinal function in CSF patients.

Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction

Compared with enalapril, sacubitril-valsartan reduces cardiovascular mortality and heart failure hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). These benefits may be related to effects on hemodynamics and cardiac remodeling. To determine whether treatment of HFrEF with sacubitril-valsartan improves central aortic stiffness and cardiac remodeling compared with enalapril. Randomized, double-blind clinical trial of 464 participants with heart failure and ejection fraction of 40% or less enrolled across 85 US sites between August 17, 2016, and June 28, 2018. Follow-up was completed on January 26, 2019. Randomization (1:1) to sacubitril-valsartan (n = 231; target dosage, 97/103 mg twice daily) vs enalapril (n = 233; target dosage, 10 mg twice daily) for 12 weeks. The primary outcome was change from baseline to week 12 in aortic characteristic impedance (Zc), a measure of central aortic stiffness. Prespecified secondary outcomes included change from baseline to week 12 in N-terminal pro-B-type natriuretic peptide, ejection fraction, global longitudinal strain, mitral annular relaxation velocity, mitral E/e' ratio, left ventricular end-systolic and end-diastolic volume indexes (LVESVI and LVEDVI), left atrial volume index, and ventricular-vascular coupling ratio. Of 464 validly randomized participants (mean age, 67.3 [SD, 9.1] years; 23.5% women), 427 completed the study. At 12 weeks, Zc decreased from 223.8 to 218.9 dyne × s/cm5 in the sacubitril-valsartan group and increased from 213.2 to 214.4 dyne × s/cm5 in the enalapril group (treatment difference, -2.2 [95% CI, -17.6 to 13.2] dyne × s/cm5; P = .78). Of 9 prespecified secondary end points, no significant between-group difference in change from baseline was seen in 4, including left ventricular ejection fraction (34%-36% with sacubitril-valsartan vs 33 to 35% with enalapril; treatment difference, 0.6% [95% CI, -0.4% to 1.7%]; P = .24). However, greater reductions from baseline were seen with sacubitril-valsartan than with enalapril in all others, including left atrial volume (from 30.4 mL/m2 to 28.2 mL/m2 vs from 29.8 mL/m2 to 30.5 mL/m2; treatment difference, -2.8 mL/m2 [95% CI, -4.0 to -1.6 mL/m2]; P < .001), LVEDVI (from 75.1 mL/m2 to 70.3 mL/m2 vs from 79.1 mL/m2 to 75.6 mL/m2; treatment difference, -2.0 mL/m2 [95% CI, -3.7 to 0.3 mL/m2]; P = .02), LVESVI (from 50.8 mL/m2 to 46.3 mL/m2 vs from 54.1 to 50.6 mL/m2; treatment difference, -1.6 mL/m2 [95% CI, -3.1 to -0.03 mL/m2]; P = .045), and mitral E/e' ratio (from 13.8 to 12.3 vs from 13.4 to 13.8; treatment difference, -1.8 [95% CI, -2.8 to -0.8]; P = .001). Rates of adverse events including hypotension (1.7% vs 3.9%) were similar in both groups. Treatment of HFrEF with sacubitril-valsartan, compared with enalapril, did not significantly reduce central aortic stiffness. The study findings may provide insight into mechanisms underlying the effects of sacubitril-valsartan in HFrEF. ClinicalTrials.gov Identifier: NCT02874794.

Arterial Remodeling and Dysfunction in the ZSF1 Rat Model of Heart Failure With Preserved Ejection Fraction.

The interplay between the stiffened heart and vessels has long been viewed as a core mechanism in heart failure with preserved ejection fraction, but the incremental vascular molecular remodeling mechanisms from systemic arterial hypertension to heart failure with preserved ejection fraction remain poorly investigated. Our aim was to characterize central arterial remodeling and dysfunction in ZSF1 obese rats and to compare it with hypertensive ZSF1 lean and healthy Wistar-Kyoto controls. Twenty-week-old male ZSF1 obese (n=9), lean (n=9), and Wistar-Kyoto rats (n=9) underwent left ventricular pressure-volume loop evaluation and synchronous acquisition of ascending aortic flow and pressure. Aortic rings underwent functional evaluation, histology, and molecular biology studies. Although mean arterial pressure, characteristic aortic impedance, and reactivity to phenylephrine were similarly increased in hypertensive ZSF1 lean and obese, only ZSF1 obese showed impaired relaxation and upward-shifted end-diastolic pressure-volume relationships despite preserved systolic function indexes, denoting heart failure with preserved ejection fraction. ZSF1 obese phenotype further showed decreased aortic compliance, increased wave reflection, and impaired direct NO donor and endothelial-mediated vasodilation which were accompanied on structural and molecular grounds by aortic media thickening, higher collagen content and collagen/elastin ratio, increased fibronectin and α-5 integrin protein expression and upregulated TGF (transforming growth factor)-β and CTGF (connective tissue growth factor) levels. Functional, molecular, and structural disturbances of central vessels and their potentially underlying pathways were newly characterized in experimental heart failure with preserved ejection fraction rendering the ZSF1 obese rat model suitable for preclinical testing.

Two-Element Fractional-Order Windkessel Model to Assess the Arterial Input Impedance.

Arterial system is completely coupled with the heart, such that the contractile state of the left ventricle and its produced central blood pressure (the pressure in the aorta) are in tune with the arterial mechanical properties. This study investigates the use of fractional-order capacitor and resistor elements to expose, and estimate the main arterial mechanical properties. We propose a simple two-element fractional-order Windkessel model that is able to capture the real aortic impedance dynamic for different cardiac physiological states. To perform a quantitative validation, in-silico ascending aortic blood pressure and flow database of 3,325 virtual subjects was used. The proposed model provides new simplified tool for "hemodynamic problem" solving, offering a pioneer way for a better understanding of vascular mechanical properties dependency on hemodynamic changes such as arterial viscoelasticity.

Early Assessment of Left Ventricular Function by Layer-Specific Strain and Its Relationship to Pulsatile Arterial Load in Patients with Coronary Slow Flow.

Previous studies reported a controversial left ventricular (LV) function impairment and pathophysiology in patients with coronary slow flow (CSF). Greater arterial load has been shown to increase aortic impedance and endothelial shear stress, potentially affecting coronary anatomy and function. We investigated LV systolic function by a new layer-specific strain technology and assessed the association between pulsatile arterial load and contractility.A total of 70 patients with CSF and 50 controls with normal coronary angiography were included in the study. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium, and epicardium (global longitudinal strain (GLS)-endo, GLS-mid, GLS-epi and GCS-endo, GCS-mid, GCS-epi) by two-dimensional speckle tracking imaging (2D-STI). Pulsatile arterial load was estimated by indexed arterial compliance (ACI). Layer-specific GLS showed a decreasing gradient from the endocardium to the epicardium in both the controls and CSF group. GLS-endo and GLS-mid in the CSF group were significantly lower than the control group (all P < 0.05). Layer-specific longitudinal strain showed a good correlation with the number of affected coronary arteries (all P < 0.05) and the mean thrombolysis in the myocardial infarction frame count (TFC) (all P < 0.05). ACI was lower in patients with CSF (P = 0.005), and ACI was correlated negatively with layer-specific GLS (all P < 0.05).Layer-specific evaluation of the LV provides an understanding of the layer-specific properties of the LV wall and the possible process of the LV impairment in patients with CSF. Greater pulsatile arterial load, as manifested by a lower ACI, is coupled with worse LV longitudinal function in patients with CSF.

Left ventricular and proximal aorta coupling in magnetic resonance imaging: aging together?

The importance of aorta-ventricular coupling in cardiovascular disease is recognized but underestimated. The contribution of the age-related decline in ascending aortic function compared with characteristic impedance and total peripheral resistance on left ventricular function and remodeling is poorly studied. Our aim was to evaluate the relation of proximal aortic distensibility and impedance with left ventricular geometry and function in asymptomatic individuals. We prospectively studied 100 subjects (47 men, 53 women, age: 20-84 yr). Aortic strain, distensibility, arch pulse wave velocity, characteristic impedance (Zc), total peripheral resistance, left ventricular (LV) volumes and mass, wall stress, and peak global circumferential myocardial strain and strain rates were determined by MRI. Central pressures were measured from tonometry. Ea/Ev, an index of vascular-ventricular coupling, and LV wall stress were preserved across age- or aortic-stiffness-stratified groups. Static and pulsatile components of aortic load were differentially associated with age. Increased total vascular resistance was associated with decreased LV strain and increased concentric remodeling [ratio of LV mass to end-diastolic volume (M/V ratio)] in all individuals. In younger individuals (<45 yr), aortic distensibility was related to LV strain and concentric remodeling (M/V ratio), whereas Zc was related to LV strain and concentric remodeling (M/V ratio) in older individuals (>45 yr). Early age-related stiffening of the ascending aorta is a component of LV afterload subsequently associated with increased aortic impedance and alterations in LV geometry, namely concentric remodeling, decreased myocardial strain, and increased stroke work such that LV wall stress and arterial-ventricular coupling are preserved. NEW & NOTEWORTHY Local flow and deformation can both be assessed with high precision noninvasively in the ascending aorta using MRI. Combined with central pressure measurement, they provide distensibility and impedance and simultaneous reference assessment of left ventricular deformation and geometry, hence a comprehensive evaluation of arterial-ventricular coupling to study physiology and disease.

Thoracic Aortic Aneurysm Growth in Bicuspid Aortic Valve Patients: Role of Aortic Stiffness and Pulsatile Hemodynamics.

BackgroundBicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. A thoracic aortic aneurysm (TAA) is present in ≈50% of BAV patients, who also have an 8‐fold higher risk of aortic dissection than the general population. Because the health of the aorta is directly reflected in its stiffness and pulsatile hemodynamics, we hypothesized that measures of aortic stiffness and arterial load would be associated with TAA growth in BAV.Methods and ResultsTwenty‐nine unoperated participants with TAA due to BAV who had serial imaging were recruited. Aortic stiffness and steady and pulsatile arterial load were evaluated with validated methods that integrate arterial tonometry with echocardiography. TAA growth was assessed retrospectively based on available imaging, blinded to hemodynamic status. Multivariable linear regression assessed associations of aortic stiffness and hemodynamic variables with TAA growth, adjusting for potential confounders. Overall, 66% of participants were men. Mean±SD for age, baseline aneurysm size, growth rate, and follow‐up time were 57.2±8.3 years, 46.9±3.6 mm, 0.75±0.81 mm/y, and 2.9±3.3 years, respectively. We found that greater aortic stiffness (β±SE for carotid‐femoral pulse wave velocity: 0.30±0.13. P=0.03) and aortic characteristic impedance (β±SE: 0.46±0.18, P=0.02), as well as lower total arterial and proximal aortic compliance (β±SE: −0.44±0.21, P=0.05, and −0.63±0.16, P=0.001, respectively) were independently associated with faster aneurysm growth.ConclusionsIn patients with TAA due to BAV, measures of greater aortic stiffness and pulsatile arterial load indicate an association with accelerated aneurysm expansion. Assessing arterial hemodynamics may be useful for risk stratification and disease monitoring in TAA patients with BAV.

75-Year-Old Man With Chest Pain and Dyspnea

75-Year-Old Man With Chest Pain and Dyspnea

Arterial Properties as Determinants of Left Ventricular Mass and Fibrosis in Severe Aortic Stenosis: Findings From ACRIN PA 4008.

BackgroundThe role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement (AVR).Methods and ResultsWe enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR. Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR. Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm5; P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR (R=−0.51; P=0.0026). The 6‐minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time (R=0.52; P=0.01).ConclusionsConsistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR. Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population.

Non-invasive Determination of Aortic Mechanical Properties and Their Effects on Left Ventricular Function Following Endovascular Abdominal Aneurysm Repair

BackgroundIncreased pulse-wave velocity (PWV) entails elevated arterial stiffness and is associated with adverse cardiovascular outcomes. Previous studies have shown PWV increases following endovascular aneurysm repair (EVAR). Animal models suggest elevated PWV following endograft deployment occurs in conjunction with decreased aortic compliance and increased aortic impedance. This could lead to unwanted effects on left ventricular (LV) function. This study evaluates the early implications of EVAR on aortic mechanics and associated LV function.Materials and methodsProspective observational study of elective EVAR for abdominal aneurysm. Transesophageal echocardiography was used to acquire LV flow and function, as well as images of the ascending aorta. Speckle tracking echocardiography (STE) software analysis allowed for determination of aortic volume change throughout the cardiac cycle. Aortic mechanics (including compliance, impedance and reflected wave analysis) and left-ventricular function (including cardiac output, hydraulic load and diastolic function) were measured pre- and post-endograft deployment.ResultsEndograft deployment resulted in no significant increase in aortic impedance. It did alter the timing of reflected waves in the aorta, with a greater positive wave being reflected during systole. This increased the hydraulic load on the LV with corresponding statistically non-significant trends for decreasing cardiac output and LV diastolic function.DiscussionSTE represents an emerging imaging modality for aortic biomechanical assessment. The increased PWV seen following EVAR may not reflect the same aortic biomechanical pathophysiology as in the non-surgical population with measures of increased arterial stiffness. The stiffer endograft does not appear to acutely increase aortic impedance, though it does alter the timing of reflected waves which may have negative effects on LV function.

A6486 Associations between Central-Pressure-Derived Aortic Flow Velocity Waveforms and Cardiovascular Adverse Events

Objectives: We have demonstrated that generation of aortic flow velocity waves from a model of aortic pressure and impedance can be achieved. In this study, we attempted to relate generated aortic flow waves with cardiovascular (CV) events. Methods: Data were collected from 165 subjects (table, age 30–83 y) at Cardiology Department, Klinikum Wels in 2008. Aortic flow waveforms were generated from aortic pressure waves (derived from tonometric radial waveforms using SphygmoCor 8.1 (AtCor Medical), based on known age-related changes in aortic impedance (J Hypertens 2016;34S1:e209–10), using mathematical relations (Matlab v2014). Calculated aortic flow indices were combined with aortic pressure indices determined during radial tonometry acquisition. Results: Angiographically documented coronary artery disease (CAD) was confirmed in 65 patients. During a follow-up duration of 4.2 years, 40 combined CV events occurred (16 deaths, 6 myocardial infarctions, 5 strokes, 17 coronary revascularizations). Ejection fraction (angiography) is directly related to pressure augmentation index (r = 0.35, p < 0.001), and inversely related to flow augmentation index (r = − 0.17, p = 0.045). Compared to patients without CAD, patients with CAD have a higher invasive aortic pulse wave velocity (8.9 vs 8.1 m/sec, p = 0.04), a lower mean flow velocity (8.8 vs 10.0 cm/s, p = 0.003), a lower flow augmentation index (−21 vs − 16.6 %, p = 0.01), and a lower pressure form factor (40.5 vs 42.6 mm Hg, p = 0.002). Flow form factor was a predictor of cardiovascular events (HR 0.89, CI 0.82–0.96, p = 0.003). Conclusion: Pressure-derived aortic flow waves can be associated with cardiac function parameters and may assist in prediction of CV events. Further study is warranted to establish its clinical values, especially where cardiac magnetic resonance is contradicted.

THORACIC AORTIC ANEURYSM GROWTH IN PATIENTS WITH BICUSPID AORTIC VALVES: ROLE OF AORTIC STIFFNESS AND PULSATILE HEMODYNAMICS

Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality, and the second most common etiology for thoracic aortic aneurysm (TAA) formation. Among BAV patients, risk of aortic dissection is increased 8-fold, and 25-year risk of aortic surgery is 25%. However, there are no clinical predictors of aneurysm growth for risk stratification. Since the health of the aortic wall is directly reflected in its stiffness, which increases pulsatile hemodynamic load due to impairment of the aorta’s pressure buffering function, we evaluated whether measures of aortic stiffness and hemodynamic load are associated with TAA growth in patients with BAV. Twenty nine participants with TAA due to BAV who had serial imaging were recruited. Aneurysm size was measured systematically by an imaging cardiologist blinded to hemodynamics, and growth rate was calculated in mm/year. Central arterial hemodynamics were non-invasively determined with validated methods that integrate arterial tonometry with echocardiography, yielding measures of aortic stiffness (aortic pulse wave velocity, aPWV), steady (systemic vascular resistance) and pulsatile hemodynamic load [aortic characteristic impedance (Zc), proximal aortic (PAC) and total arterial (TAC) compliances, central systolic (cSBP) and pulse pressures, forward (Pf) and reflected pressure wave amplitudes]. Spearman correlation coefficients were calculated between TAA growth rate and brachial blood pressure, as well as the aforementioned central hemodynamic measures. Multivariable linear regression adjusted for potential confounders (Table 1 legend) assessed the independent associations of hemodynamic variables with TAA growth. Sixty six percent of participants were men. Mean±standard deviation (SD) age, baseline aneurysm size and follow-up time were 57.2±8.3 years, 46.9±3.6 mm and 2.9±3.3 years, respectively. There were significant correlations between several measures of aortic stiffness and pulsatile arterial load with TAA growth (Table1, top). There were no significant correlations between brachial blood pressure parameters or steady hemodynamic load with TAA growth (P>0.05 for each). In multivariable linear regression, measures of aortic stiffness (aPWV) and pulsatile hemodynamic load (Zc, PAC, TAC) remained independently associated with aneurysm growth (Table 1, bottom). Other hemodynamic measures were not independently associated with TAA growth. In patients with TAA due to BAV, greater aortic stiffness and central pulsatile hemodynamic load are associated with faster aneurysm growth; while brachial blood pressure and steady hemodynamic load are not. Our findings suggest that evaluating aortic stiffness and pulsatile arterial load could be useful for risk stratification of subjects with TAA due to BAV, and may provide a therapeutic target for this disease.

Comparing square root method of measuring the cardiac output by means of aortic impedance change component to Kubicek's method.

The aim of this study is to explore a calculated method used to measure the cardiac output using the aortic impedance change component of reconstructed impedance cardiography. Routine impedance cardiography was measured using Kubicek's method with four ring electrodes. The thoracic mixed impedance changes were measured by six leads, which consisted of 15 electrodes. The aortic impedance change component was separated from six thoracic mixed impedance changes through waveform reconstruction. The square root formula used to calculate the cardiac output was deduced based on the thoracic impedance change equation and the aortic volume change hypothesis during the systole period. The cardiac outputs of 180 normal adults and 72 patients with cardiac insufficiency who could still walk freely were contrastively computed with both Kubicek's formula and the square root formula. For 180 normal adults, the cardiac index (CI) computed with the square root formula was 3.60 ± 0.45 L/min/m2 , with normal values ranging from 2.7 to 4.5 L/min/m2 . A total of 163 cases (90.6%) had a CI in the standard range (2.7-4.3 L/min/m2 ) adopted in clinical applications. The CI computed with Kubicek's formula was 3.61 ± 0.86 L/min/m2 , with normal values ranging from 1.9 to 5.3 L/min/m2 , and only 115 cases (63.9%) had a CI in the above standard range. Among the 72 patients with cardiac insufficiency, 20 (27.8%) patients had a CI < 2.0 L/min/m2 with Kubicek's formula. Of these 20 cases, 9 cases had a CI < 1.5 L/min/m2 , and 4 cases had a CI < 1.1 L/min/m2 . In contrast, none of the 72 patients had a CI < 2.0 L/min/m2 with the square root formula. In addition, the influence of the chest circumference on the CI was lower for the square root formula than for Kubicek's formula. The CI calculated with the square root formula had a better normal value range, was more accurate for the patients with cardiac insufficiency, and was less affected by the chest circumference than the CI calculated with Kubicek's formula.

Influence of age and gender on blood pressure variability and baroreflex sensitivity in a healthy population in the Indian sub-continent.

Background The current exploratory study was aimed at estimating measures of blood pressure variability (BPV) and baroreflex sensitivity (BRS) in a healthy population in the Indian sub-continent. Methods One hundred and forty-two healthy subjects were recruited for the study. Blood pressure (BP) was recorded continuously for 15 min using the Finometer (Finapres Medical Systems, The Netherlands). For offline analysis, Nevrokard cardiovascular parameter analysis (CVPA) software (version 2.1.0) was used for BPV analysis. BRS was determined by spectral and sequence methods. One-way ANOVA and Bonferroni's test were used to compare parameters. Pearson's correlation coefficient was employed to look for possible associations between age and other continuous variables. Results Out of 196 screened volunteers, 54 were excluded and 142 subjects were grouped based on ages as 10-19 years (group 1), 20-29 years (group 2), 30-39 years (group 3), 40-49 years (group 4), and 50-59 years (group 5). Within groups, body mass index (BMI, p=0.000) and BP (systolic and diastolic) were significantly different. Post hoc analysis showed mean blood pressure (MBP) and diastolic blood pressure (DBP) differing significantly between groups 1 and 4 (p<0.05 for both) along with other cardiovascular parameters. Age correlated positively with BMI and all parameters of BP. Significant gender differences were observed for stroke volume, cardiac output, up BRS, total BRS, peripheral resistance (PR), and aortic impedance. Conclusions Our study has provided reference values for BPV and BRS in an Indian population. It also indicates age-related neurocardiac imbalance and possible utility of these tests for screening at the start of neurocardiac damage in a healthy population.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P=0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P<0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function.

Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts.

The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance) to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF) of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks). Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy) and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%), rather than on anatomical features (average decrease ~60%), to achieve compensation of pump function in the early phase of heart failure.

Voluntary liquorice ingestion increases blood pressure via increased volume load, elevated peripheral arterial resistance, and decreased aortic compliance

We investigated the haemodynamic effects of two-week liquorice exposure (glycyrrhizin dose 290–370 mg/day) in 22 healthy volunteers during orthostatic challenge. Haemodynamics were recorded during passive 10-minute head-up tilt using radial pulse wave analysis, whole-body impedance cardiography, and spectral analysis of heart rate variability. Thirty age-matched healthy subjects served as controls. Liquorice ingestion elevated radial systolic (p < 0.001) and diastolic (p = 0.018) blood pressure and systemic vascular resistance (p = 0.037). During orthostatic challenge, heart rate increased less after the liquorice versus control diet (p = 0.003) and low frequency power of heart rate variability decreased within the liquorice group (p = 0.034). Liquorice intake increased central pulse pressure (p < 0.001) and augmentation index (p = 0.002) supine and upright, but in the upright position the elevation of augmentation index was accentuated (p = 0.007). Liquorice diet also increased extracellular fluid volume (p = 0.024) and aortic to popliteal pulse wave velocity (p = 0.027), and aortic characteristic impedance in the upright position (p = 0.002). To conclude, in addition to increased extracellular fluid volume and large arterial stiffness, two weeks of liquorice ingestion elevated systemic vascular resistance and augmentation index. Measurements performed at rest may underestimate the haemodynamic effects of liquorice ingestion, as enhanced central wave reflection and reduced chronotropic response were especially observed in the upright position.