Total Arterial Compliance Research Articles

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.

A comprehensive characterization of myocardial and vascular phenotype in pediatric chronic kidney disease using cardiovascular magnetic resonance imaging

BackgroundChildren with chronic kidney disease (CKD) have increased cardiovascular mortality. Identifying high-risk children who may benefit from further therapeutic intervention is difficult as cardiovascular abnormalities are subtle. Although transthoracic echocardiography may be used to detect sub-clinical abnormalities, it has well-known problems with reproducibility that limit its ability to accurately detect these changes. Cardiovascular magnetic resonance (CMR) is the reference standard method for assessing blood flow, cardiac structure and function. Furthermore, recent innovations enable the assessment of radial and longitudinal myocardial velocity, such that detection of sub-clinical changes is now possible. Thus, CMR may be ideal for cardiovascular assessment in pediatric CKD. This study aims to comprehensively assess cardiovascular function in pediatric CKD using CMR and determine its relationship with CKD severity.MethodsA total of 120 children (40 mild, 40 moderate, 20 severe pre-dialysis CKD subjects and 20 healthy controls) underwent CMR with non-invasive blood pressure (BP) measurements. Cardiovascular parameters measured included systemic vascular resistance (SVR), total arterial compliance (TAC), left ventricular (LV) structure, ejection fraction (EF), cardiac timings, radial and longitudinal systolic and diastolic myocardial velocities. Between group comparisons and regression modelling were used to identify abnormalities in CKD and determine the effects of renal severity on myocardial function.ResultsThe elevation in mean BP in CKD was accompanied by significantly increased afterload (SVR), without evidence of arterial stiffness (TAC) or increased fluid overload. Left ventricular volumes and global function were not abnormal in CKD. However, there was evidence of LV remodelling, prolongation of isovolumic relaxation time and reduced systolic and diastolic myocardial velocities.ConclusionAbnormal cardiovascular function is evident in pre-dialysis pediatric CKD. Novel CMR biomarkers may be useful for the detection of subtle abnormalities in this population. Further studies are needed to determine to prognostic value of these biomarkers.

Systemic arteriosclerosis is associated with left ventricular remodeling but not atherosclerosis: a TASCFORCE study

BackgroundArteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk.MethodsOne thousand six hundred fifty-one subjects free of clinical cardiovascular disease and with a < 20% 10 year cardiovascular risk score underwent a cardiovascular magnetic resonance (CMR) study and whole body CMR angiogram. Arteriosclerosis was measured using total arterial compliance (TAC) - calculated as the indexed stroke volume divided by the pulse pressure. Atherosclerosis was quantified using a standardised atheroma score (SAS) which was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Left ventricular remodelling was measured using left ventricular mass to volume ratio (LVMVR).ResultsOne thousand five hundred fifteen (38% male, 53.8 ± 8.2 years old) completed the study. On univariate analysis TAC was associated with SAS but this was lost after accounting for cardiovascular risk factors in both males (B = − 0.001 (− 0.004–0.002),p = 0.62) and females (B = 0.000(95%CI -0.002--0.002),p = 0.78). In contrast compliance correlated with LVMVR after accounting for cardiovascular risk factors (B = − 0.12(95%CI -0.16--0.091),p < 0.001 in males; B = − 0.12(95%CI -0.15--0.086),p < 0.001 in females).ConclusionSystemic arteriosclerosis is associated with left ventricular remodelling but not atherosclerosis. Future efforts in cardiovascular risk prevention should thus seek to address both arteriosclerosis and atherosclerosis individually.

Ventriculo-Arterial Coupling Analysis Predicts the Hemodynamic Response to Norepinephrine in Hypotensive Postoperative Patients: A Prospective Observational Study.

The objectives of the present study were to evaluate, in patients with persistent arterial hypotension in the immediate postcardiac surgery period, the effects of norepinephrine infusion on ventriculo-arterial coupling, its determinants: arterial elastance and end-systolic ventricular elastance, and to test the ability of arterial elastance to end-systolic ventricular elastance ratio to predict stroke volume increases. Prospective observational study. Cardiac-vascular surgical ICU. Twenty-eight postoperative cardiac surgery patients, in whom physicians decided to administer norepinephrine infusion, were included. Arterial pressure, stroke volume index, cardiac index, indexed total peripheral resistance, arterial compliance, arterial elastance, and end-systolic ventricular elastance, were measured before and after norepinephrine infusion. We estimated ventriculo-arterial coupling by the arterial elastance to end-systolic ventricular elastance ratio and defined stroke volume responders by a stroke volume increase greater than or equal to 15%. Twenty-two of the 28 subjects had altered ventriculo-arterial coupling (1.87 [1.57-2.51] vs 1.1 [1-1.18]). Fifteen of the 28 subjects (54%) were stroke volume responders. At baseline, stroke volume responders had similar arterial pressure, higher indexed total peripheral resistance, arterial elastance, arterial elastance to end-systolic ventricular elastance ratio (2.21 [1.69-2.89] vs 1.33 [1.1-1.56]; p < 0.05), and lower arterial compliance, indexed total peripheral resistance and cardiac index. Norepinephrine significantly increased arterial pressure in all subjects. In stroke volume responders, norepinephrine increased arterial elastance, end-systolic ventricular elastance, cardiac index, and improved arterial elastance/end-systolic ventricular elastance coupling. The baseline arterial elastance to end-systolic ventricular elastance ratio predicted stroke volume responsiveness (area under the curve [95% CI], 0.87 [0.71-1]; p < 0.0001). In patients with arterial hypotension norepinephrine increased end-systolic ventricular elastance and arterial elastance. The effects of norepinephrine on stroke volume depend on baseline ventriculo-arterial coupling. Although norepinephrine infusion corrects arterial hypotension in all subjects, increase of stroke volume occurred only in subjects with altered ventriculo-arterial coupling.

Identifying Hemodynamic Determinants of Pulse Pressure: A Combined Numerical and Physiological Approach.

We examined the ability of a simple reduced model comprising a proximal characteristic impedance linked to a Windkessel element to accurately predict central pulse pressure (PP) from aortic blood flow, verified that parameters of the model corresponded to physical properties, and applied the model to examine PP dependence on cardiac and vascular properties. PP obtained from the reduced model was compared with theoretical values obtained in silico and measured values in vivo. Theoretical values were obtained using a distributed multisegment model in a population of virtual (computed) subjects in which cardiovascular properties were varied over the pathophysiological range. In vivo measurements were in normotensive subjects during modulation of physiology with vasoactive drugs and in hypertensive subjects. Central PP derived from the reduced model agreed with theoretical values (mean difference±SD, -0.09±1.96 mm Hg) and with measured values (mean differences -1.95±3.74 and -1.18±3.67 mm Hg for normotensive and hypertensive subjects, respectively). Parameters extracted from the reduced model agreed closely with theoretical and measured physical properties. Central PP was seen to be determined mainly by total arterial compliance (inversely associated with central arterial stiffness) and ventricular dynamics: the blood volume ejected by the ventricle into the aorta up to time of peak pressure and blood flow into the aorta (corresponding to the rate of ventricular ejection) up to this time point. Increased flow and volume accounted for 20.1 mm Hg (52%) of the 39.0 mm Hg difference in PP between the upper and lower tertiles of the hypertensive subjects.

Arterial Stiffness Is Associated With QTc Interval Prolongation in Patients With Heart Failure.

A prolonged corrected QT (QTc) interval is a known risk factor for adverse cardiac events. Understanding the determinants and physiologic correlates of QTc is necessary for selecting proper strategies to reduce the risk of adverse events in high-risk patients. We sought to evaluate the role of arterial stiffness in heart failure as a determinant of QTc prolongation. This was an observational study that recruited ambulatory heart failure patients (New York Heart Association Classes I-II) from an outpatient heart failure clinic. In the supine resting position, consented patients underwent noninvasive 12-lead electrocardiograph (ECG) and hemodynamic monitoring using BioZ Dx impedance cardiography. ECGs were evaluated by a reviewer blinded to clinical data, and QTc interval was automatically computed. Patients with pacing or bundle branch block (BBB) were analyzed separately. Strengths of associations were evaluated using Pearson's r coefficients and multivariate linear regression. The final sample ( N = 44) was 62 ± 13 years of age and 64% male with ejection fraction of 34% ± 12%. At univariate level, QTc interval moderately ( r > .50) correlated with cardiac output, left cardiac work index, systemic vascular resistance, and total arterial compliance in patients with intrinsically narrow QRS complexes. At the multivariate level, increasing systemic vascular resistance and decreasing total arterial compliance remained independent predictors of widening QTc interval in this group ( R2 = .54). No significant correlations were seen in patients with pacing or BBB. In the absence of conduction abnormalities, magnitude of arterial stiffness, an indirect measure of endothelial dysfunction, is associated with QTc interval prolongation.

Arterial stiffness, sex, and age difference on hypertensive response to supine bicycle exercise.

Contributors to a hypertensive response to exercise (HTR) according to sex and age have not been fully evaluated. The authors analyzed a database of supine bicycle exercise stress echocardiography findings. HTR was defined as peak systolic blood pressure ≥210mmHg for men and ≥190mmHg for women during exercise. A total of 797 patients (306 [38%] women) were analyzed, with a mean age of 64±10years. Female sex, hypertension; higher left ventricular ejection fraction, effective arterial elastance, and pulse wave velocity; and lower total arterial compliance were significantly related to HTR. Patients with HTR had higher relative wall thickness, ratio of early diastolic mitral inflow and annular velocity, and diastolic elastance (all P≤.05). In multivariable analysis, indices of arterial stiffness such as pulse wave velocity, arterial elastance, total arterial compliance, and systemic vascular resistance were more strongly related in women, while in men, index of sympathetic activation was additionally related to HTR (all P≤.05). Female sex and lower total arterial compliance in older patients (≥65years) and higher systemic vascular resistance and left ventricular relative wall thickness in younger patients were more strongly related to HTR. In conclusion, HTR was related to arterial stiffness, sympathetic activation, and diastolic dysfunction; however, the associations were different according to sex and age, which might guide individualized therapy.

Influence of critical closing pressure on systemic vascular resistance and total arterial compliance: A clinical invasive study

Systemic vascular resistance (SVR) and total arterial compliance (TAC) modulate systemic arterial load, and their product is the time constant (Tau) of the Windkessel. Previous studies have assumed that aortic pressure decays towards a pressure asymptote (P∞) close to 0mmHg, as right atrial pressure is considered the outflow pressure. Using these assumptions, aortic Tau values of ∼1.5seconds have been documented. However, a zero P∞ may not be physiological because of the high critical closing pressure previously documented in vivo. To calculate precisely the Tau and P∞ of the Windkessel, and to determine the implications for the indices of systemic arterial load. Aortic pressure decay was analysed using high-fidelity recordings in 16subjects. Tau was calculated assuming P∞=0mmHg, and by two methods that make no assumptions regarding P∞ (the derivative and best-fit methods). Assuming P∞=0mmHg, we documented a Tau value of 1372±308ms, with only 29% of Windkessel function manifested by end-diastole. In contrast, Tau values of 306±109 and 353±106ms were found from the derivative and best-fit methods, with P∞ values of 75±12 and 71±12mmHg, and with ∼80% completion of Windkessel function. The "effective" resistance and compliance were ∼70% and ∼40% less than SVR and TAC (area method), respectively. We did not challenge the Windkessel model, but rather the estimation technique of model variables (Tau, SVR, TAC) that assumes P∞=0. The study favoured a shorter Tau of the Windkessel and a higher P∞ compared with previous studies. This calls for a reappraisal of the quantification of systemic arterial load.

PP.06.10] BLOOD PRESSURE VARIABILITY AND TARGET ORGAN DAMAGE IN HYPERTENSION

Objective: Hypertension is associated with several markers of subclinical target organ damage (TOD). Short-term blood pressure variability (SBPV) is a prognostic factor for cardiovascular events in hypertensives. We hypothesized that there is a relationship between SBPV and TOD in never-treated hypertensives. Design and method: We enrolled 943 consecutive essential hypertensives (mean age 53 ± 12 years, 497 males). Markers of subclinical TOD [left ventricular mass index (LVMI), pulse wave velocity (PWV), total arterial compliance (TAC), ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR)] and 24-h ambulatory blood pressure were evaluated in all patients. LVMI was assessed echocardiographically using the Devereux formula. Carotid-femoral PWV was estimated with the Complior. eGFR was calculated by the Cockcroft-Gault formula. ABI was calculated by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. The ratio of stroke volume to pulse pressure was measured echocardiographically as a surrogate of TAC. SBPV was calculated as follows: 1) SD of 24-hour, daytime, or nighttime SBP and 2) weighted SD of 24-hour SBP. Results: In multivariable regression analysis, all four variables of SBPV exhibited significant association with LVMI (p = 0.014, p = 0.002, p = 0.002 and p < 0.001, respectively), PWV (p = 0.021, p = 0.015, p = 0.055 and p = 0.006, respectively) and TAC (p = 0.048, p = 0.020, p = 0.036 and p = 0.006, respectively). In multivariable analysis, ABI and eGFR were not associated with indices of SBPV. We assessed TOD based on 2013 European Guidelines for Hypertension [left ventricular hypertrophy (LVMI>115 g/m2 in men and >95 g/m2 in women), increased PWV (PWV>10m/s), decreased ABI (ABI<0.9) and decreased renal function (eGFR<60 ml/min)]. In multivariable logistic regression analysis, SBPV indices were not associated with markers of TOD (P > 0.05). Conclusions: Our findings support a complex relationship between SBPV and TOD in hypertension. Specifically, SBPV is more closely related to markers of ventricular and vascular compliance than other markers of TOD in hypertension.

PP.14.15] ASSOCIATION BETWEEN VENTRICULAR-ARTERIAL COUPLING PARAMETERS AND LEFT ATRIAL REMODELING WITH ATRIAL FIBRILLATION RECURRENCES IN PATIENTS WITH DIASTOLIC DYSFUNCTION

Objective: Left ventricular diastolic dysfunction (DD) is one of the main mechanisms of structural and functional changes of the left atrium (LA). It can be caused by impaired ventricular-arterial coupling (VAC). The relationships between VAC, LA remodeling and atrial fibrillation (AF), however, remain unclear. We tried to evaluate VAC parameters with LA remodeling and their predictive value for AF recurrence during a 3-month follow-up period in patients with recurrent AF and mild to moderate left ventricular DD. Design and method: Sixty patients [45% male, median age 65 (61; 72) years] with recurrent non-valvular AF and mild to moderate DD were enrolled in the study and treated with amiodarone 200 mg + metoprolol 50 mg daily (n = 30) or sotalol 160 mg daily (n = 30). All the patients underwent conventional and speckle tracking echocardiography. Global peak LA longitudinal strain (PALS) and strain rate (PALSR) in the reservoir (r) and contractile (c) phases were assessed using 6 segments in the 4-chamber and 2-chamber views. To assess VAC EaI, EesI, Ea/Ees, systemic vascular resistance index and total arterial compliance (TAC) were calculated. Follow-up period was 3 months. Results: EaI was significantly associated with LA size (r = −0.38, p = 0.003), LA end diastolic volume (r = −0.33, p = 0.009) and PALSc (r = −0.31, p = 0.02). EesI correlated with E/A (r = −0.3, p = 0.02). Ea/Ees was related to E/E’ (r = 0.4, p = 0.002). Thirty-five (58%) patients (group 1) had complete antiarrhythmic response, whereas 25 (42%) patients (group 2) experienced at least one AF recurrence. Despite having comparable E/E’, E’ and LA volume index, the patients of group 1 had significantly higher PALSr (15.7 vs 12.6, p = 0.004), PALSc (−16.2 vs -13.9, p = 0.008), PALSRr (2.44 vs 1.76, p < 0,001), PALSRc (−2.4 vs −1.66, p < 0.001), E (0.87 vs 0.69, p < 0.001), IVRT (90 vs 89, p = 0.04) and TAC (1.26 vs 1.08, p = 0.04), whereas Ees corrected by afterload was higher in group 2 (619 vs 803, p = 0,004). Stepwise multiple regression analysis revealed that PALSRc was linked to AF recurrence (β = 0.38, p = 0.04). Conclusions: VAC parameters were significantly related to LA remodeling and DD but had no prognostic value in recurrence of AF. Only PALSRc was independently associated with complete antiarrhythmic effect.

Hemodynamic Response to Nitroprusside in Patients With Low-Gradient Severe Aortic Stenosis and Preserved Ejection Fraction

BackgroundLow-gradient severe aortic stenosis (LGSAS) with preserved ejection fraction (EF) is incompletely understood. The influence of arterial afterload and diastolic dysfunction on the hemodynamic presentation of LGSAS remains unknown. ObjectivesThe authors sought to determine the acute hemodynamic response to sodium nitroprusside in LGSAS with preserved EF. MethodsSymptomatic patients with LGSAS and preserved EF underwent cardiac catheterization with comparison of hemodynamic measurements before and after nitroprusside. ResultsForty-one subjects (25 with low flow [LF], stroke volume index [SVI] ≤35 ml/m2, 16 with normal flow [NF]) were included. At baseline, LF patients had lower total arterial compliance (0.36 ± 0.12 ml/m2/mm Hg vs. 0.48 ± 0.16 ml/m2/mm Hg; p = 0.01) and greater effective arterial elastance (2.77 ± 0.84 mm Hg · m2/ml vs. 1.89 ± 0.82 mm Hg · m2/ml; p = 0.002). In all patients, nitroprusside reduced elastance, left ventricular filling pressures, and pulmonary artery pressures and improved compliance (p < 0.05). Aortic valve area increased to ≥1.0 cm2 in 6 LF (24%) and 4 NF (25%) subjects. Change in SVI with nitroprusside varied inversely to baseline SVI and demonstrated improvement in LF only (3 ± 6 ml/m2; p = 0.02). ConclusionsNitroprusside reduces afterload and left ventricular filling pressures in patients with LGSAS and preserved EF, enabling reclassification to moderate stenosis in 25% of patients. An inverse relationship between baseline SVI and change in SVI with afterload reduction was observed, suggesting that heightened sensitivity to afterload is a significant contributor to LF-LGSAS pathophysiology. These data highlight the utility of afterload reduction in the diagnostic assessment of LGSAS.

Role of peripheral vascular resistance as an indicator of cardiovascular abnormalities in patients with Parkinson's disease.

The aim of this study was to evaluate cardiovascular autonomic modulation in response to an orthostatic stress in healthy subjects and Parkinson's disease (PD). The study included 47 controls and 56 PD patients divided into groups (vasoconstrictor PD, vasodilator PD, control) according to vasodilation/vasoconstriction response during 70° head up tilt test. Using impedance cardiography (ICG) and electrocardiography (ECG) we measured stroke volume, cardiac output, left ventricular work index, left ventricular ejection time, acceleration index, index of contractility, Heather index, thoracic fluid content, total peripheral resistance, total arterial compliance. We also analyzed heart rate variability (HRV), using spectral analysis and continuous blood pressure (contBP). At rest, the vasodilator PD group showed significantly higher values of total peripheral resistance and lower values of stroke volume and cardiac output, compared to the vasoconstrictor PD and the control groups. A post-tilt drop in ∆ (change rest - tilt) systolic blood pressure, ∆mean blood pressure, ∆total peripheral resistance and ∆Heather index, and a significantly lower increase in ∆diastolic blood pressure was observed in subjects from the vasodilator PD group compared to the vasoconstrictor PD and the control groups. No statistically significant differences were observed for HRV parameters between the vasoconstrictor and vasodilator PD groups, P>.05. Longer duration and higher disease stage of PD correlated with a reduction in post-tilt systolic blood pressure changes in vasodilator group. Positive inotropy of the cardiac muscle represents a significant factor preventing orthostatic hypotension in PD subjects with a concurrent drop in peripheral vascular resistance during orthostatic stress.

Influence of beat-to-beat blood pressure variability on vascular elasticity in hypertensive population

Whether elevated beat-to-beat blood pressure variability (BPV) has an influence on vascular elasticity is confounded and poorly understood. This study hypothesized that the increased BPV could have an adverse effect on the vascular elasticity, as estimated by total arterial compliance (TAC), independent of blood pressure (BP) values. Beat-to-beat BP and TAC were measured in 81 hypertensive patients (experimental population) and in 80 normal adults (control population). Beat-to-beat BPV was assessed by standard deviation (SD), average real variability (ARV), residual standard deviation (RSD) and variation independent of mean (VIM). In experimental population, systolic BPV (SBPV) showed a significant correlation with TAC (SD, r = −0.326, p < 0.001; ARV, r = −0.277, p = 0.003; RSD, r = −0.382, p < 0.001; VIM, r = −0.274, p = 0.003); similarly, SD, RSD and VIM of diastolic BP (DBP) also showed explicit correlation with TAC (r = −0.255, p = 0.006; r = −0.289, p = 0.002; r = −0.219, p = 0.019; respectively). However, in the control population, neither SBPV nor diastolic BPV (DBPV) showed a significant correlation with TAC. Furthermore, in the experimental population, VIM of systolic BP (SBP) was also a determinant of TAC (β = −0.100, p = 0.040) independent of average SBP, DBP, age and body mass index. In conclusion, these data imply that beat-to-beat BPV, especially SBPV, shows an independent correlation with vascular elasticity in hypertensive population.

Arterial Stiffening With Exercise in Patients With Heart Failure and Preserved Ejection Fraction

BackgroundAortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). ObjectivesThis study compared indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive control subjects to examine their relationships to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite. MethodsA total of 22 hypertensive control subjects and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis to measure oxygen consumption. Invasively measured radial artery pressure waveforms were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection. ResultsArterial load and wave reflections in HFpEF were similar to those in control subjects at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures in control subjects. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both p < 0.0001). With peak exercise, increased wave reflections, impaired compliance, and increased resistance and elastance were observed in subjects with HFpEF. A subset of HFpEF subjects (n = 52) received sodium nitrite or placebo therapy in a 1:1 double-blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance and elastance and central hemodynamics during exercise. ConclusionsAbnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF. (Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease [EXEC]; NCT01418248. Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction; NCT01932606. Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction; NCT02262078)

Norepinephrine reduces arterial compliance less than phenylephrine when treating general anesthesia‐induced arterial hypotension

During general anesthesia, arterial hypotension is frequent and may be an important contributor to perioperative morbidity. We assessed the effect of a 5μg bolus of Norepinephrine (NA) when compared with 50μg bolus of Phenylephrine (PE) administered to treat hypotension during maintenance anesthesia, on MAP, derived cardiac output and arterial stiffness parameters. Patients scheduled for a neurosurgical procedure under general anesthesia were prospectively included. Monitoring included invasive blood pressure, esophageal Doppler, and arterial tonometer used to estimate central aortic pressure with arterial stiffness parameters, such as augmentation index (Aix). After initial resuscitation, hypotensive episodes were corrected by a bolus administration of NA or PE in a peripheral venous line. There were 269 bolus administrations of vasopressors (149 NA, 120 PE) in 47 patients with no adverse effects detected. A decrease in stroke volume (SV) was observed with PE compared with NA (-18±9% vs. -14±7%, P<0.001). This decrease was associated with an increase in Aix, which was greater for PE than for NA (+10±8% vs. +6±6%, P<0.0001), and a decrease in total arterial compliance greater for PE compared to NA (Ctot=SV/Central Pulse Pressure) (-35±9% vs. -29±10%, P<0.001). This study suggests that 5μg of NA administered as a bolus in a peripheral venous line could treat general anesthesia-induced arterial hypotension with a smaller decrease in SV and arterial compliance when compared to PE.

Total arterial compliance, estimated by a novel method, is better related to left ventricular mass compared to aortic pulse wave velocity: The SAFAR study

ABSTRACTAim: The investigation of the association between total arterial compliance (CT)—estimated by a novel technique—with left ventricular mass (LVM) and hypertrophy (LVH). Our hypothesis was that CT may be better related to LVM compared to the gold-standard regional aortic stiffness. Within the frame of the ongoing cross-sectional study “SAFAR,” 226 subjects with established hypertension or with suspected hypertension underwent blood pressure (BP) assessment, carotid-to-femoral pulse wave velocity (cf-PWV), and echocardiographic measurement of LVM. LVM index (LVMI) was calculated by the ratio of LVM to body surface area. CT was estimated by a previously proposed and validated formula: CT = 36.7 /cf-PWV2 [ml/mmHg]. LVMI was related to age (r = 0.207, p = 0.002), systolic BP (r = 0.248, p < 0.001), diastolic BP (r = 0.139, p = 0.04), mean BP (r = 0.212, p = 0.002), pulse pressure (r = 0.212, p = 0.002), heart rate (r = −0.172, p = 0.011), cf-PWV (r = 0.268, p < 0.001), and CT (r = −0.317, p < 0.001). The highest correlation was observed for CT that was significantly stronger than the respective correlation of cf-PWV (p < 0.001). In multivariate analysis, CT was a stronger determinant, compared to cf-PWV, of LVMI and LVH. It remains to be further explored whether CT has also a superior prognostic value beyond and above local or regional (segmental) estimates of pulse wave velocity.

Abnormal Wave Reflections and Left Ventricular Hypertrophy Late After Coarctation of the Aorta Repair.

Patients with repaired coarctation of the aorta are thought to have increased afterload due to abnormalities in vessel structure and function. We have developed a novel cardiovascular magnetic resonance protocol that allows assessment of central hemodynamics, including central aortic systolic blood pressure, resistance, total arterial compliance, pulse wave velocity, and wave reflections. The main study aims were to (1) characterize group differences in central aortic systolic blood pressure and peripheral systolic blood pressure, (2) comprehensively evaluate afterload (including wave reflections) in the 2 groups, and (3) identify possible biomarkers among covariates associated with elevated left ventricular mass (LVM). Fifty adult patients with repaired coarctation and 25 age- and sex-matched controls were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal-resolution spiral phase-contrast cardiovascular magnetic resonance flow sequence. These data were used to derive central hemodynamics and to perform wave intensity analysis noninvasively. Covariates associated with LVM were assessed using multivariable linear regression analysis. There were no significant group differences (P≥0.1) in brachial systolic, mean, or diastolic BP. However central aortic systolic blood pressure was significantly higher in patients compared with controls (113 versus 107 mm Hg, P=0.002). Patients had reduced total arterial compliance, increased pulse wave velocity, and larger backward compression waves compared with controls. LVM index was significantly higher in patients than controls (72 versus 59 g/m2, P<0.0005). The magnitude of the backward compression waves was independently associated with variation in LVM (P=0.01). Using a novel, noninvasive hemodynamic assessment, we have shown abnormal conduit vessel function after coarctation of the aorta repair, including abnormal wave reflections that are associated with elevated LVM.

Association between beat-to-beat blood pressure variability and vascular elasticity in normal young adults during the cold pressor test.

The beat-to-beat blood pressure (BP) monitoring parameters, such as average beat-to-beat BP, BP variability (BPV), could have an influence on the vascular elasticity. This study hypothesized that the elevated beat-to-beat BPV could evoke the reduction of the vascular elasticity independent of BP levels. We measured the beat-to-beat BP recordings and total arterial compliance (TAC), which was used to assess the vascular elasticity, in 80 young healthy adults during the cold pressor test (CPT). The CPT included 3 phases: baseline phase, cold stimulus phase, recovery phase. Six parameters were used to estimate BPV. In bivariate correlation analysis, TAC showed a significant correlation with systolic BP (SBP) and diastolic BP (DBP) in the cold stimulus phase; and 4 indices of SBP variability (SBPV) were associated with TAC (r = 0.271∼0.331, P ≤ 0.015) in the recovery phase; similarly, 2 indices of DBP variability (DBPV) were also correlated with TAC (r = 0.221∼0.285, P ≤ 0.048) in the recovery phase. In multivariate regression analysis, DBPV (β = 0.229, P = 0.001) was a determinant of TAC independent of average DBP, sex, and weight. In addition, both beat-to-beat BP and BPV values increased in the cold stimulus phase (P < 0.01); whereas, the TAC decreased in the cold stimulus phase (P < 0.01). In conclusion, these data suggest that the beat-to-beat DBPV shows an independent association with the vascular elasticity in young normal adults during the CPT.

Beat-by-beat assessment of cardiac afterload using descending aortic velocity-pressure loop during general anesthesia: a pilot study.

Continuous cardiac afterload evaluation could represent a useful tool during general anesthesia (GA) to titrate vasopressor effect. Using beat to beat descending aortic pressure(P)/flow velocity(U) loop obtained from esophageal Doppler and femoral pressure signals might allow to track afterload changes. Methods We defined three angles characterizing the PU loop (alpha, beta and Global After-Load Angle (GALA)). Augmentation index (AIx) and total arterial compliance (Ctot) were measured via radial tonometry. Peripheral Vascular Resistances (PVR) were also calculated. Twenty patients were recruited and classified into low and high cardiovascular (CV) risk group. Vasopressors were administered, when baseline mean arterial pressure (MAP) fell by 20%. Results We studied 118 pairs of pre/post bolus measurements. At baseline, patients in the lower CV risk group had higher cardiac output (6.1 ± 1.7 vs 4.2 ± 0.6L min; p = 0.005), higher Ctot (2.7 ± 1.0 vs 2.0 ± 0.4ml/mmHg, p = 0.033), lower AIx and PVR (13 ± 10 vs 32 ± 11% and 1011 ± 318 vs 1390 ± 327dyns/cm5; p < 0.001 and p = 0.016, respectively) and lower GALA (41 ± 15 vs 68 ± 6°; p < 0.001). GALA was the only PU Loop parameter associated with Ctot, AIx and PVR. After vasopressors, MAP increase was associated with a decrease in Ctot, an increase in AIx and PVR and an increase in alpha, beta and GALA (p < 0.001 for all). Changes in GALA and Ctot after vasopressors were strongly associated (p = 0.004). Conclusions PU Loop assessment from routine invasive hemodynamic optimization management during GA and especially GALA parameter could monitor cardiac afterload continuously in anesthetized patients, and may help clinicians to titrate vasopressor therapy.

Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance

BackgroundLeft ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta.MethodsCMR was performed in 121 patients, 2–4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m−2), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance).ResultsAt 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m2.L−1, EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6–month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular obstruction at baseline (EDV-/EF-: 37%, EDV+/EF-: 76%, EDV-/EF+: 38%, EDV+/EF+: 73%, p = 0.003).ConclusionLV remodeling following reperfused MI is strongly influenced by the variable decrease in systemic vascular resistance under standard care vasodilating medication. The CMR monitoring of vascular resistance may help to tailor these medications for improving vascular resistance and consequently, LV ejection fraction.Trial registrationNCT01109225 on ClinicalTrials.gov site (April, 2010).