Non-invasive evaluation of left ventricular afterload, part 2 : arterial pressure-flow and pressure-volume relations in humans

The mechanical load imposed by the systemic circulation to the left ventricle is an important determinant of normal and abnormal cardiovascular function. Left ventricular afterload is determined by complex time-varying phenomena, which affect pressure and flow patterns generated by the pumping ventricle. Left ventricular afterload is best described in terms of pressure-flow relations, allowing for quantification of various components of load using simplified biomechanical models of the circulation, with great potential for mechanistic understanding of the role of central hemodynamics in cardiovascular disease and the effects of therapeutic interventions. In the second part of this tutorial, we review analytic methods used to characterize left ventricular afterload, including analyses of central arterial pressure-flow relations and windkessel modeling (pressure-volume relations). Conceptual descriptions of various models and methods are emphasized over mathematical ones. Our review is aimed at helping researchers and clinicians obtain and interpret results from analyses of left ventricular afterload in clinical and epidemiological settings

A unified mechanism for the water hammer pulse and pulsus bisferiens in severe aortic regurgitation: Insights from wave intensity analysis

The carotid bisferiens pulse and the radial water hammer pulse are typical of severe chronic aortic regurgitation. Little is known about the mechanism of these classic cardiovascular signs identified on physical examination. We report the first characterization of these abnormal pulse patterns using wave intensity analysis (WIA) in a patient with severe aortic regurgitation. We demonstrate that an abnormally pronounced forward-traveling mid-systolic suction wave, which immediately followed the initial forward-traveling compression wave from ventricular contraction, explained these pulse patterns. This suction wave likely resulted from blood inertia, arising from a ventricle ejecting a very large stroke volume into a vasodilated arterial tree. Our report demonstrates a novel pulsatile hemodynamic mechanism that unifies the pathogenesis of the bisferiens pulse and the water-hammer pulse in severe aortic regurgitation. (C) 2017 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved

Misinterpretation of the determinants of elevated forward wave amplitude inflates the role of the proximal aorta

Background: The hemodynamic basis for increased pulse pressure (PP) with aging remains controversial. The classic paradigm attributes a predominant role to increased pulse wave velocity (PWV) and premature wave reflections (WRs). A controversial new paradigm proposes increased forward pressure wave amplitude (FWA), attributed to proximal aortic characteristic impedance (Z(c)), as the predominant factor, with minor contributions from WRs. Based on theoretical considerations, we hypothesized that (rectified) WRs drive the increase in FWA, and that the forward pressure wave does not depend solely on the interaction between flow and Z(c) (QZc product). Methods and Results: We performed 3 substudies: (1) open-chest anesthetized dog experiments (n=5); (2) asymmetric T-tube model-based study; and (3) human study in a diverse clinical population (n=193). Animal experiments demonstrated that FWA corresponds to peak QZc only when WRs are minimal. As WRs increased, FWA was systematically greater than QZc and peaked well after peak flow, analogous to late-systolic peaking of pressure attributable to WRs. T-tube modeling confirmed that increased/ premature WRs resulted in increased FWA. Magnitude and timing of WRs explained 80.8% and 74.3% of the variability in the difference between FWA and peak QZc in dog and human substudies, respectively. Conclusions: Only in cases of minimal reflections does FWA primarily reveal the interaction between peak aortic flow and proximal aortic diameter/stiffness. FWA is strongly dependent on rectified reflections. If interpreted out of context with the hemodynamic principles of its derivation, the FWA paradigm inappropriately amplifies the role of the proximal aorta in elevation of FWA and PP

Impact of diabetes mellitus on ventricular structure, arterial stiffness, and pulsatile hemodynamics in heart failure with preserved ejection fraction

Background-Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HFpEF, but its impact on left ventricular and arterial structure and function in HFpEF is unknown. Methods and Results-Weassessed the impact of diabetesmellitus on left ventricular cellular and interstitial hypertrophy (assessedwith cardiacmagnetic resonance imaging, including T1mapping pregadolinium and postgadolinium administration), arterial stiffness (assessed with arterial tonometry), and pulsatile arterial hemodynamics (assessed with in-office pressure-flow analyses and 24-hour ambulatory monitoring) among 53 subjects with HFpEF (32 diabetic and 21 nondiabetic subjects). Despite few differences in clinical characteristics, diabetic subjects with HFpEF exhibited a markedly greater left ventricular mass index (78.1 [95% CI, 70.4-85.9] g versus 63.6 [95% CI, 55.8-71.3] g; P=0.0093) and indexed extracellular volume (23.6 [95% CI, 21.2-26.1] mL/m(2) versus 16.2 [95% CI, 13.1-19.4] mL/m(2); P=0.0008). Pronounced aortic stiffening was also observed in the diabetic group (carotid-femoral pulse wave velocity, 11.86 [95% CI, 10.4-13.1] m/s versus 8.8 [95% CI, 7.5-10.1] m/s; P=0.0027), with an adverse pulsatile hemodynamic profile characterized by increased oscillatory power (315 [95% CI, 258-373] mWversus 190 [95% CI, 144-236] mW; P=0.0007), aortic characteristic impedance (0.154 [95% CI, 0.124-0.183] mmHg/mL per second versus 0.096 [95% CI, 0.072-0.121] mm Hg/mL per second; P=0.0024), and forward (59.5 [95% CI, 52.8-66.1] mm Hg versus 40.1 [95% CI, 31.6-48.6] mm Hg; P=0.0010) and backward (19.6 [95% CI, 16.2-22.9] mm Hg versus 14.1 [95% CI, 10.9-17.3] mm Hg; P=0.0169) wave amplitude. Abnormal pulsatile hemodynamics were also evident in 24-hour ambulatory monitoring, despite the absence of significant differences in 24-hour systolic blood pressure between the groups. Conclusions-Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile hemodynamics, and ventricular-arterial interactions in HFpEF

Early and late systolic wall stress differentially relate to myocardial contraction and relaxation in middle-aged adults: the Asklepios study

Experimental studies implicate late systolic load as a determinant of impaired left ventricular (LV) relaxation. We aimed to assess the relationship between the myocardial loading sequence and left ventricular (LV) contraction and relaxation. Time-resolved central pressure and time-resolved LV geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1,214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity, systolic annular velocities were measured with tissue Doppler imaging and segmentaveraged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, gender and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (e', standardized β=-0.25; P<0.0001) and mitral inflow propagation velocity (Vpe, standardized β=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with e' (standardized β=0.18; P<0.0001) and Vpe (standardized β=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (S', standardized β=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized β=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher S' (standardized β=0.16; P=0.002) and greater longitudinal strain (standardized β=-0.24; P=0.002). The loading sequence remained independently associated with e' after adjustment for S' or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of LV systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation

Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction

Objective: Increased penetration of pulsatile power to the brain has been implicated in the pathogenesis of age-related cognitive dysfunction and dementia, a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). However, there is a lack of knowledge on the effects of organic and inorganic nitrates administration in this population on the power carried by pressure and flow waves traveling through the proximal aorta and penetrating the carotid artery into the brain microvasculature. Approach: We assessed aortic and carotid hemodynamics non-invasively in two sub-studies: (1) at baseline and after administration of 0.4 mg of sublingual nitroglycerine (an organic nitrate; n = 26); and (2) in a randomized controlled trial of placebo (PB) versus inorganic nitrate administration (beetroot-juice (BR), 12.9 mmol NO3; n = 16). Main results: Wave and hydraulic power analysis demonstrated that NTG increased total hydraulic power (from 5.68% at baseline to 8.62%, P = 0.001) and energy penetration (from 8.69% to 11.63%; P = 0.01) from the aorta to the carotid, while inorganic nitrate administration did not induce significant changes in aortic and carotid wave power (power: 5.49% PB versus 6.25% BR, P = 0.49; energy: 8.89% PB versus 10.65% BR, P = 0.27). Significance: Organic nitrates, but not inorganic nitrates, increase the amount of hydraulic energy transmitted into the carotid artery in subjects with HFpEF. These findings may have implications for the adverse effect profiles of these agents (such as the differential incidence of headaches) and for the pulsatile hemodynamic stress of the brain microvasculature in this patient population

Late systolic central hypertension as a predictor of incident heart failure : the Multi-Ethnic Study of Atherosclerosis

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure. Methods and Results: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/ESPTI) was assessed as a predictor of incident HF during median 8.5 years of follow-up. The L/ESPTI was predictive of incident HF (hazard ratio per 1% increase= 1.22; 95% CI= 1.15 to 1.29; P58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI= 0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001). Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population

Non-invasive intraventricular pressure differences estimated with cardiac MRI in subjects without heart failure and with heart failure with reduced and preserved ejection fraction

Objective Non-invasive assessment of left ventricular (LV) diastolic and systolic function is important to better understand physiological abnormalities in heart failure (HF). The spatiotemporal pattern of LV blood flow velocities during systole and diastole can be used to estimate intraventricular pressure differences (IVPDs). We aimed to demonstrate the feasibility of an MRI-based method to calculate systolic and diastolic IVPDs in subjects without heart failure (No-HF), and with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods We studied 159 subjects without HF, 47 subjects with HFrEF and 32 subjects with HFpEF. Diastolic and systolic intraventricular flow was measured using two-dimensional in-plane phase-contrast MRI. The Euler equation was solved to compute IVPDs in diastole (mitral base to apex) and systole (apex to LV outflow tract). Results Subjects with HFpEF demonstrated a higher magnitude of the early diastolic reversal of IVPDs (-1.30 mm Hg) compared with the No-HF group (-0.78 mm Hg) and the HFrEF group (-0.75 mm Hg; analysis of variance p=0.01). These differences persisted after adjustment for clinical variables, Doppler-echocardiographic parameters of diastolic filling and measures of LV structure (No-HF=-0.72; HFrEF=-0.87; HFpEF=-1.52 mm Hg; p=0.006). No significant differences in systolic IVPDs were found in adjusted models. IVPD parameters demonstrated only weak correlations with standard Doppler-echocardiographic parameters. Conclusions Our findings suggest distinct patterns of systolic and diastolic IVPDs in HFpEF and HFrEF, implying differences in the nature of diastolic dysfunction between the HF subtypes