Reliability of effective arterial elastance using peripheral arterial pressure as surrogate for left ventricular end-systolic pressure.

To compare the effective arterial elastance (Ea) obtained from the arterial pressure with Ea calculated from left-ventricular (LV) pressure-volume analysis. Experimental study. LV pressure-volume data was obtained with a conductance catheter and arterial pressures were measured via a fluid-filled catheter placed in the proximal aorta, femoral and radial arteries. Ea was calculated as LV end-systolic pressure (ESP)/stroke volume (SV). Experimental protocol consisted sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid), and contractility (esmolol/dobutamine). 90% of systolic pressure (Eaao_SYS, Eafem_SYS, Earad_SYS), mean arterial pressure (Eaao_MAP, Eafem_MAP, Earad_MAP), and dicrotic notch pressure (Eaao_DIC, Eafem_DIC, Earad_DIC) were used as surrogates for LV ESP. SV was calculated from the LV pressure-volume data. When Ea was compared with estimations based on 90% SAP, the relationship was r2 = 0.95, 0.94 and 0.92; and the bias and limits of agreement (LOA): - 0.01 ± 0.12, - 0.09 ± 0.12, - 0.05 ± 0.15 mmHg ml-1, for Eaao_SYS, Eafem_SYS and Earad_SYS, respectively. For estimates using dicrotic notch, the relationship was r2 = 0.94, 0.95 and 0.94 for Eaao_DIC, Eafem_DIC and Earad_DIC, respectively; with a bias and LOA: 0.05 ± 0.11, 0.06 ± 0.12, 0.10 ± 0.12 mmHg ml-1, respectively. When Ea was compared with estimates using MAP, the relationship was r2 = 0.95, 0.96 and 0.95 for Eaao_MAP, Eafem_MAP and Earad_MAP, respectively; with a bias and LOA: 0.05 ± 0.11, 0.06 ± 0.11, 0.06 ± 0.11 mmHg ml-1, respectively. LV ESP can be estimated from the arterial pressure. Provided that the SV measurement is reliable, the ratio MAP/SV provides a robust Ea surrogate over a wide range of hemodynamic conditions and is interchangeably in any peripheral artery, so it should be recommended as an arterial estimate of Ea in further research.

Prognostic Value of Right Ventricular Afterload in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Pulmonary hypertension (PH) and secondary mitral regurgitation (MR) are associated with adverse outcomes after mitral transcatheter edge-to-edge repair. We aim to study the prognostic value of invasively measured right ventricular afterload in patients undergoing mitral transcatheter edge-to-edge repair. METHODS AND RESULTS: We identified patients who underwent right heart catheterization ≤1 month before transcatheter edge-to-edge repair. The end points were all-cause mortality and a composite of mortality and heart failure hospitalization at 2 years. Using the receiver operating characteristic curve-derived threshold of 0.6 for pulmonary effective arterial elastance ([Ea], pulmonary artery systolic pressure/stroke volume), patients were stratified into 3 profiles based on PH severity (low elastance [HE]: Ea <0.6/mean pulmonary artery pressure (mPAP)) <35; High Elastance with No/Mild PH (HE-): Ea ≥0.6/mPAP <35; and HE with Moderate/Severe PH (HE+): Ea ≥0.6/mPAP ≥35) and MR pathogenesis (Primary MR [PMR])/low elastance, PMR/HE, and secondary MR). The association between this classification and clinical outcomes was examined using Cox regression. Among 114 patients included, 50.9% had PMR. Mean±SD age was 74.7±10.6 years. Patients with Ea ≥0.6 were more likely to have diabetes, atrial fibrillation, New York Heart Association III/IV status, and secondary MR (all P<0.05). Overall, 2-year cumulative survival was 71.1% and was lower in patients with secondary MR and mPAP ≥35. Compared with patients with low elastance, cumulative 2-year event-free survival was significantly lower in HE- and HE+ patients (85.5% versus 50.4% versus 41.0%, respectively, P=0.001). Also, cumulative 2-year event-free survival was significantly higher in patients with PMR/low elastance when compared with PMR/HE and patients with secondary mitral regurgitation (85.5% versus 55.5% versus 46.1%, respectively, P=0.005). CONCLUSIONS: Assessment of the preprocedural cardiopulmonary profile based on mPAP, MR pathogenesis, and Ea guides patient selection by identifying hemodynamic features that indicate likely benefit from mitral-transcatheter edge-to-edge repair in PH or lack thereof.

Arterial Baroreflex Inhibits Muscle Metaboreflex Induced Increases in Effective Arterial Elastance: Implications for Ventricular-Vascular Coupling.

The ventricular-vascular relationship assesses the efficacy of energy transferred from the left ventricle to the systemic circulation and is quantified as the ratio of effective arterial elastance to maximal left ventricular elastance. This relationship is maintained during exercise via reflex increases in cardiovascular performance raising both arterial and ventricular elastance in parallel. These changes are, in part, due to reflexes engendered by activation of metabosensitive skeletal muscle afferents-termed the muscle metaboreflex. However, in heart failure, ventricular-vascular uncoupling is apparent and muscle metaboreflex activation worsens this relationship through enhanced systemic vasoconstriction markedly increasing effective arterial elastance which is unaccompanied by substantial increases in ventricular function. This enhanced arterial vasoconstriction is, in part, due to significant reductions in cardiac performance induced by heart failure causing over-stimulation of the metaboreflex due to under perfusion of active skeletal muscle, but also as a result of reduced baroreflex buffering of the muscle metaboreflex-induced peripheral sympatho-activation. To what extent the arterial baroreflex modifies the metaboreflex-induced changes in effective arterial elastance is unknown. We investigated in chronically instrumented conscious canines if removal of baroreflex input via sino-aortic baroreceptor denervation (SAD) would significantly enhance effective arterial elastance in normal animals and whether this would be amplified after induction of heart failure. We observed that effective arterial elastance (Ea), was significantly increased during muscle metaboreflex activation after SAD (0.4 ± 0.1 mmHg/mL to 1.4 ± 0.3 mmHg/mL). In heart failure, metaboreflex activation caused exaggerated increases in Ea and in this setting, SAD significantly increased the rise in Ea elicited by muscle metaboreflex activation (1.3 ± 0.3 mmHg/mL to 2.3 ± 0.3 mmHg/mL). Thus, we conclude that the arterial baroreflex does buffer muscle metaboreflex induced increases in Ea and this buffering likely has effects on the ventricular-vascular coupling.

Right Ventricular Dysfunction During Endurance Exercise as Determined by Pressure-Volume Analysis.

A 37-year-old athlete completed invasive endurance (90 km) bicycle exercise testing for right ventricular pressure-volume analysis. Increased right ventricular afterload caused declines in ventricular-arterial coupling and cardiac output, causing increased arteriovenous oxygen difference to maintain oxygen uptake. These findings demonstrate effects of changes in right ventricular performance on exercise capacity. (Level of Difficulty: Intermediate.).

Predictive value of change in effective arterial elastance in norepinephrine weaning: a retrospective study.

BACKGROUND: The weaning of vasopressors is usually an empirical choice made by clinicians. The aim of this study is to assess the predictive value of change in effective arterial elastance (ΔEa%) induced by fluid administration in early initiation of norepinephrine (NE) weaning. METHODS: Included were intensive care unit (ICU) septic shock patients with an indwelling pulmonary artery catheter who experienced initial resuscitation and required a fluid challenge. Reduced norepinephrine dose or maintained steady (ΔNE ≤0 µg/min) at 6 hours after inclusion (T6) was defined as early initiation of norepinephrine weaning. Univariate and multivariate analyses were performed to assess ΔEa% viability and other hemodynamic parameters in predicting the possibility of norepinephrine weaning. A receiver operating characteristic (ROC) analysis was used to confirm model predictions. RESULTS: One hundred and eight patients were assessed. Of 108 patients, 75 (69.4%) constituted the NE weaning group at T6. The multivariate analysis showed that ΔEa% [odds ratios (OR): 0.95; 95% confidence interval (CI): 0.89-0.99; P=0.003] was an independent predictive factor for norepinephrine weaning at T6. ROC analysis confirmed that ΔEa% was associated with norepinephrine weaning [area under ROC curve (AUC) at 0.64; 95% CI: 0.52-0.75; P=0.026]. To predict norepinephrine weaning, the optimum threshold for ΔEa% was 5.1% (sensitivity: 61%, specificity: 67%). Notably, the combination of ΔEa%, change in systemic vascular resistance (ΔSVR%) and change in cardiac output (ΔCO%) strengthened the predictive ability with an AUC at 0.73 (95% CI: 0.64-0.83; P=0.001). Median (interquartile range) duration (in hours) of norepinephrine was significantly shorter in the NE weaning group compared with the NE worsening group {48 [34-89] vs. 72 [54-90] hours, P=0.048}. CONCLUSIONS: Change in effective arterial elastance induced by fluid administration may assist clinicians in detecting patients who is possible to initiate norepinephrine weaning. Early initiation of norepinephrine weaning was associated with shorter duration of norepinephrine exposure.

Invasive Cardiomechanics During Transcatheter Edge-to-Edge Repair for Massive Tricuspid Regurgitation Using Biventricular Pressure-Volume Loop Monitoring.

Invasive pressure-volume loop analysis allows direct monitoring of changing intraventricular cardiac mechanics during structural heart interventions. Our aim was to illustrate changes in right and left ventricular mechanics during transcatheter edge-to-edge tricuspid repair for severe tricuspid regurgitation. (Level of Difficulty: Advanced.).

Susceptibility to high-altitude pulmonary edema is associated with increased pulmonary arterial stiffness during exercise.

High-altitude pulmonary edema (HAPE), a reversible form of capillary leak, is a common consequence of rapid ascension to high altitude and a major cause of death related to high-altitude exposure. Individuals with a prior history of HAPE are more susceptible to future episodes, but the underlying risk factors remain uncertain. Previous studies have shown that HAPE-susceptible subjects have an exaggerated pulmonary vasoreactivity to acute hypoxia, but incomplete data are available regarding their vascular response to exercise. To examine this, seven HAPE-susceptible subjects and nine control subjects (HAPE-resistant) were studied at rest and during incremental exercise at sea level and at 3,810 m altitude. Studies were conducted in both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) conditions at each location. Here, we report an expanded analysis of previously published data, including a distensible vessel model that showed that HAPE-susceptible subjects had significantly reduced small distal artery distensibility at sea level compared with HAPE-resistant control subjects [0.011 ± 0.001 vs. 0.021 ± 0.002 mmHg-1; P < 0.001). Moreover, HAPE-susceptible subjects demonstrated constant distensibility over all conditions, suggesting that distal arteries are maximally distended at rest. Consistent with having increased distal artery stiffness, HAPE-susceptible subjects had greater increases in pulmonary artery pulse pressure with exercise, which suggests increased proximal artery stiffness. In summary, HAPE-susceptible subjects have exercise-induced increases in proximal artery stiffness and baseline increases in distal artery stiffness, suggesting increased pulsatile load on the right ventricle.NEW & NOTEWORTHY In comparison to subjects who appear resistant to high-altitude pulmonary edema, those previously symptomatic show greater increases in large and small artery stiffness in response to exercise. These differences in arterial stiffness may be a risk factor for the development of high-altitude pulmonary edema or evidence that consequences of high-altitude pulmonary edema are long-lasting after return to sea level.

Revisiting the relationship between left ventricular ejection fraction and ventricular-arterial coupling.

The aim of this article was to analyse in-depth the relationship between left ventricular (LV) ejection fraction (EF) (LVEF) and the most commonly used formulas for the calculation of LV elastance (Ees), volume intercept at 0 mmHg pressure (V0), effective arterial elastance (Ea), and ventricular-arterial coupling (VAC) as are validated today. We analyse the mathematical resulting consequences, raising the question on the physiological validity. To our knowledge, some of the following mathematical consequences have never been published. On the basis of studies demonstrating that normal LV dimensions and LVEF have a Gaussian unimodal distribution, we considered that the normal modal LVEF is 62% or very close to it. Expressed as a fraction, it is 0.62, that is, the reciprocal of the Phi number (namely, 1/Φ ~ 0.618). Applying Euclid's mathematical law on the extreme and mean ratio (the golden ratio), we studied the LVEF-VAC relationship in normal hearts. The simplification of the VAC formula (with V0 = 0) leads to false physiological results; V0 extraction from single-beat Chen's formula leads to high negative results in normal subjects; based on the Euclid law, LVEF and Ea/Ees will be equal for a ratio value of 0.618 (62%) where V0 cannot be different from 0 mL; LVEF and VAC inverse relationship formula (Ea/Ees = 1/LVEF - 1) is reducible to a fundamental property of Phi: 1/Φ = (Φ - 1), being valid only if LVEF = VAC at a 0.618 value; according to this restriction, Vo can only be 0 mL, thus describing a very limited range. The Ea/Ees ratio, owing to its mathematical more dynamic behaviour, can be more sensitive than LVEF, being a valuable clinical tool in patients with heart failure (HF) with reduced EF, acute unstable haemodynamic situations, where Ees and Ea variations are disproportionate. However, the application is doubtful in HF with preserved EF where Ees and Ea may have same-direction augmentation. The modified VAC formula suffers from oversimplification, reducing it to a dimensionless ratio, which is supposed to approximate non-linear time-varying functions. Thus, we advocate for caution and in-depth understanding when using simplified formulas in clinical practice.

Dynamic Arterial Elastance as a Ventriculo-Arterial Coupling Index: An Experimental Animal Study.

Dynamic arterial elastance (Eadyn), the ratio between arterial pulse pressure and stroke volume changes during respiration, has been postulated as an index of the coupling between the left ventricle (LV) and the arterial system. We aimed to confirm this hypothesis using the gold-standard for defining LV contractility, afterload, and evaluating ventricular-arterial (VA) coupling and LV efficiency during different loading and contractile experimental conditions. Twelve Yorkshire healthy female pigs submitted to three consecutive stages with two opposite interventions each: changes in afterload (phenylephrine/nitroprusside), preload (bleeding/fluid bolus), and contractility (esmolol/dobutamine). LV pressure-volume data was obtained with a conductance catheter, and arterial pressures were measured via a fluid-filled catheter in the proximal aorta and the radial artery. End-systolic elastance (Ees), a load-independent index of myocardial contractility, was calculated during an inferior vena cava occlusion. Effective arterial elastance (Ea, an index of LV afterload) was calculated as LV end-systolic pressure/stroke volume. VA coupling was defined as the ratio Ea/Ees. LV efficiency (LVeff) was defined as the ratio between stroke work and the LV pressure-volume area. Eadyn was calculated as the ratio between the aortic pulse pressure variation (PPV) and conductance-derived stroke volume variation (SVV). A linear mixed model was used for evaluating the relationship between Ees, Ea, VA coupling, LVeff with Eadyn. Eadyn was inversely related to VA coupling and directly to LVeff. The higher the Eadyn, the higher the LVeff and the lower the VA coupling. Thus, Eadyn, an easily measured parameter at the bedside, may be of clinical relevance for hemodynamic assessment of the unstable patient.

Vascular-ventricular coupling during exercise is not affected by exaggerated blood pressures in endurance-trained athletes.

This study sought to examine whether cardiovascular performance during exercise, assessed using the vascular-ventricular coupling index (VVC), was affected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. Subjects were middle-aged endurance-trained men and women. Blood pressure measurements and left ventricular echocardiography were performed in a semiupright position at rest and during steady-state cycling at workloads that elicited 100-110 beats/min (stage 1) and 130-140 beats/min (stage 2). These data were used to calculate effective arterial elastance index (EaI), left ventricular end-systolic elastance index (ELVI), and their ratio (VVC). Additional measurements of left ventricular volumes and function (i.e., stroke volume, cardiac output, and longitudinal strain) and indirect assessments of peripheral vascular function (i.e., total arterial compliance and peripheral vascular resistance) were examined. Fourteen subjects with EBP (EBP+, 50% men) and 14 sex-matched subjects without EBP (EBP-) participated, with results presented as EBP+ versus EBP-. EaI and ELVI increased from rest to exercise while VVC decreased, but only ELVI was different between groups at stage 1 [7.6 (1.8) vs. 6.4 (1.0) mmHg·ml-1·m-2, P = 0.045] and stage 2 [10.3 (1.6) vs. 8.0 (1.7) mmHg·ml-1·m-2, P < 0.001]. Additional comparisons revealed no group difference in the contribution of the Frank-Starling mechanism or left ventricular and peripheral vascular function during exercise. The cardiovascular adjustment to exercise in athletes with EBP is achieved through a matched increase in both EaI and ELVI, and the absence of between-group differences in left ventricular or peripheral vascular function suggests that other factors may contribute to the EBP response.NEW & NOTEWORTHY Cardiovascular performance during submaximal exercise, assessed using vascular-ventricular coupling, is unaffected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. The underlying mechanisms of EBP in athletes remain unknown as changes in left ventricular and peripheral vascular function during exercise were similar in athletes with and without EBP.

A Large Animal Model of Right Ventricular Failure due to Chronic Thromboembolic Pulmonary Hypertension: A Focus on Function.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease that progresses to right ventricular (RV) failure and death if left untreated. Little is known regarding the progression of RV failure in this disease, greatly limiting effective prognoses, and therapeutic interventions. Large animal models enable the use of clinical techniques and technologies to assess progression and diagnose failure, but the existing large animal models of CTEPH have not been shown to replicate the functional consequences of the RV, i.e., RV failure. Here, we created a canine embolization model of CTEPH utilizing only microsphere injections, and we used a combination of right heart catheterization (RHC), echocardiography (echo), and magnetic resonance imaging (MRI) to quantify RV function. Over the course of several months, CTEPH led to a 6-fold increase in pulmonary vascular resistance (PVR) in four adult, male beagles. As evidenced by decreased cardiac index (0.12 ± 0.01 v. 0.07 ± 0.01 [L/(min*kg)]; p < 0.05), ejection fraction (0.48 ± 0.02 v. 0.31 ± 0.02; p < 0.05), and ventricular-vascular coupling ratio (0.95 ± 0.09 v. 0.45 ± 0.05; p < 0.05), as well as decreased tricuspid annular plane systolic excursion (TAPSE) (1.37 ± 0.06 v. 0.86 ± 0.05 [cm]; p < 0.05) and increased end-diastolic volume index (2.73 ± 0.06 v. 2.98 ± 0.02 [mL/kg]; p < 0.05), the model caused RV failure. The ability of this large animal CTEPH model to replicate the hemodynamic consequences of the human disease suggests that it could be utilized for future studies to gain insight into the pathophysiology of CTEPH development, following further optimization.

Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model.

Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology. Despite comparable increases in RV systolic pressure (Col1a1(+/+): 46 ± 2 mmHg; Col1a1(R/R): 47 ± 3 mmHg), the impaired collagen degradation in Col1a1(R/R) mice resulted in no RV collagen accumulation, limited RV hypertrophy, and maintained right ventricular-pulmonary vascular coupling with HySu exposure. The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in RV remodeling in response to chronic pressure overload. Our results suggest novel treatments that reduce collagen turnover may offer a new therapeutic strategy for PAH patients.

Right ventricular afterload sensitivity dramatically increases after left ventricular assist device implantation: A multi-center hemodynamic analysis.

BACKGROUND: Right ventricular (RV) failure is a source of morbidity and mortality after left ventricular assist device (LVAD) implantation. In this study we sought to define hemodynamic changes in afterload and RV adaptation to afterload both early after implantation and with prolonged LVAD support. METHODS: We reviewed right heart catheterization (RHC) data from participants who underwent continuous-flow LVAD implantation at our institutions (n = 244), excluding those on inotropic or vasopressor agents, pulmonary vasodilators or additional mechanical support at any RHC assessment. Hemodynamic data were assessed at 5 time intervals: (1) pre-LVAD (within 6 months); (2) early post-LVAD (0 to 6 months); (3) 7 to 12 months; (4) 13 to 18 months; and (5) very late post-LVAD (18 to 36 months). RESULTS: Sixty participants met the inclusion criteria. All measures of right ventricular load (effective arterial elastance, pulmonary vascular compliance and pulmonary vascular resistance) improved between the pre- and early post-LVAD time periods. Despite decreasing load and pulmonary artery wedge pressure (PAWP), RAP remained unchanged and the RAP:PAWP ratio worsened early post-LVAD (0.44 [0.38, 0.63] vs 0.77 [0.59, 1.0], p < 0.001), suggesting a worsening of RV adaptation to load. With continued LVAD support, both RV load and RAP:PAWP decreased in a steep, linear and dependent manner. CONCLUSIONS: Despite reducing RV load, LVAD implantation leads to worsened RV adaptation. With continued LVAD support, both RV afterload and RV adaptation improve, and their relationship remains constant over time post-LVAD. These findings suggest the RV afterload sensitivity increases after LVAD implantation, which has major clinical implications for patients struggling with RV failure.

Simultaneous pressure-volume measurements using optical sensors and MRI for left ventricle function assessment during animal experiment.

Simultaneous pressure and volume measurements enable the extraction of valuable parameters for left ventricle function assessment. Cardiac MR has proven to be the most accurate method for volume estimation. Nonetheless, measuring pressure simultaneously during MRI acquisitions remains a challenge given the magnetic nature of the widely used pressure transducers. In this study we show the feasibility of simultaneous in vivo pressure-volume acquisitions with MRI using optical pressure sensors. Pressure-volume loops were calculated while inducing three inotropic states in a sheep and functional indices were extracted, using single beat loops, to characterize systolic and diastolic performance. Functional indices evolved as expected in response to positive inotropic stimuli. The end-systolic elastance, representing the contractility index, the diastolic myocardium compliance, and the cardiac work efficiency all increased when inducing inotropic state enhancement. The association of MRI and optical pressure sensors within the left ventricle successfully enabled pressure-volume loop analysis after having respective data simultaneously recorded during the experimentation without the need to move the animal between each inotropic state.

Effective arterial elastance is insensitive to pulsatile arterial load.

Effective arterial elastance (E(A)) was proposed as a lumped parameter that incorporates pulsatile and resistive afterload and is increasingly being used in clinical studies. Theoretical modeling studies suggest that E(A) is minimally affected by pulsatile load, but little human data are available. We assessed the relationship between E(A) and arterial load determined noninvasively from central pressure-flow analyses among middle-aged adults in the general population (n=2367) and a diverse clinical population of older adults (n=193). In a separate study, we investigated the sensitivity of E(A) to changes in pulsatile load induced by isometric exercise (n=73). The combination of systemic vascular resistance and heart rate predicted 95.6% and 97.8% of the variability in E(A) among middle-aged and older adults, respectively. E(A) demonstrated a quasi-perfect linear relationship with the ratio of systemic vascular resistance/heart period (middle-aged adults, R=0.972; older adults, R=0.99; P<0.0001). Aortic characteristic impedance, total arterial compliance, reflection magnitude, and timing accounted together for <1% of the variability in E(A) in either middle-aged or older adults. Despite pronounced changes in pulsatile load induced by isometric exercise, changes in E(A) were not independently associated with changes pulsatile load but were rather a nearly perfect linear function of the ratio of systemic vascular resistance/heart period (R=0.99; P<0.0001). Our findings demonstrate that E(A) is simply a function of systemic vascular resistance and heart rate and is negligibly influenced by (and insensitive to) changes in pulsatile afterload in humans. Its current interpretation as a lumped parameter of pulsatile and resistive afterload should thus be reassessed.

Ventricular-arterial coupling: Invasive and non-invasive assessment.

Interactions between the left ventricle (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. Ventricularearterial coupling is most frequently assessed in the pressure-volume plane using the ratio of effective arterial elastance (EA) to LV end-systolic elastance (EES). EA (usually interpreted as a lumped index of arterial load) can be computed as end-systolic pressure/stroke volume, whereas EES (a load-independent measure of LV chamber systolic stiffness and contractility) is ideally assessed invasively using data from a family of pressure-volume loops obtained during an acute preload alteration. Single-beat methods have also been proposed, allowing for non-invasive estimations of EES using simple echocardiographic measurements. The EA/EES ratio is useful because it provides information regarding the operating mechanical efficiency and performance of the ventricular-arterial system. However, it should be recognized that analyses in the pressure-volume plane have several limitations and that "ventricular-arterial coupling" encompasses multiple physiologic aspects, many of which are not captured in the pressure-volume plane. Therefore, additional assessments provide important incremental physiologic information about the cardiovascular system and should be more widely used. In particular, it should be recognized that: (1) comprehensive analyses of arterial load are important because EA poorly characterizes pulsatile LV load and does not depend exclusively on arterial properties; (2) The systolic loading sequence, an important aspect of ventricular-arterial coupling, is neglected by pressure-volume analyses, and can profoundly impact LV function, remodeling and progression to heart failure. This brief review summarizes methods for the assessment of ventricular-arterial interactions, as discussed at the Artery 12 meeting (October 2012).

Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients.

OBJECTIVES: The study aimed to determine whether isolated heart rate (HR) reduction with ivabradine reduces afterload of patients with systolic heart failure. BACKGROUND: The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden. METHODS: Among the patients with systolic heart failure (ejection fraction ≤35%) randomized to either placebo or ivabradine in the SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial), 275 patients (n = 132, placebo; n = 143, ivabradine 7.5 mg twice a day) were included in the echocardiographic substudy. Ea, total arterial compliance (TAC), and end-systolic elastance (Ees) were calculated at baseline and after 8 months of treatment. Blood pressure was measured by arm cuff; stroke volume (SV), ejection fraction, and end-diastolic volume were assessed by echocardiography. RESULTS: At baseline Ea, TAC, HR, and Ees did not differ significantly between ivabradine- and placebo-treated patients. After 8 months of treatment, HR was significantly reduced in the ivabradine group (p < 0.0001) and was accompanied by marked reduction in Ea (p < 0.0001) and improved TAC (p = 0.004) compared with placebo. Although contractility remained unchanged, ventricular-arterial coupling was markedly improved (p = 0.002), resulting in a higher SV (p < 0.0001) in the ivabradine-treated patients. CONCLUSIONS: Isolated HR reduction by ivabradine improves TAC, thus reducing Ea. Because Ees is unaltered, improved ventricular-arterial coupling is responsible for increased SV. Therefore, unloading of the heart may contribute to the beneficial effect of isolated HR reduction in patients with systolic heart failure.

Left ventricular efficiency after ligation of patent ductus arteriosus for premature infants.

OBJECTIVE: The purpose of this study was to evaluate the hemodynamic changes in left ventricular function before and after patent ductus arteriosus ligation in premature infants with regard to the energetic efficiency of left ventricular pumping. METHODS: Thirty-five premature infants who underwent patent ductus arteriosus ligation were enrolled in this study. Left ventricular efficiency was evaluated at 4 points: within 24 hours before patent ductus arteriosus ligation, within 24 hours after patent ductus arteriosus ligation, between postoperative days 2 and 4, and on postoperative day 7. The indices of contractility (end-systolic elastance) and afterload (effective arterial elastance) were approximated on the basis of the systemic blood pressure and systolic or diastolic left ventricular volume. The ratio of stroke work and pressure-volume area, representing the ventricular efficiency, was estimated using the following theoretic formula: the ratio of stroke work and pressure-volume area = 1/(1 + 0.5 ventriculoarterial coupling). RESULTS: Left ventricular efficiency was transiently deteriorated within 24 hours after patent ductus arteriosus ligation because of the marked increase of the afterload and the slight increase of contraction, and then recovered to preoperation levels by 2 to 4 days after patent ductus arteriosus ligation. CONCLUSIONS: Analysis of indices representing the afterload, contractility, and energetic efficiency of the left ventricle may provide practical information for the management of premature infants during the postoperative period after patent ductus arteriosus ligation.