Erez Nevo

Estimation of Central Aortic Pressure Waveform by Mathematical Transformation of Radial Tonometry Pressure Validation of Generalized Transfer Function

BACKGROUND Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although they often differ substantially from central pressures, they may be mathematically transformed to approximate the latter. We tested this approach, examining intersubject and intrasubject variability and the validity of using a single averaged transformation, which would enhance its applicability. METHODS AND RESULTS Invasive central aortic pressure by micromanometer and radial pressure by automated tonometry were measured in 20 patients at steady state and during hemodynamic transients (Valsalva maneuver, abdominal compression, nitroglycerin, or vena caval obstruction). For each patient, transfer functions (TFs) between aortic and radial pressures were calculated by parametric model and results averaged to yield individual TFs. A generalized TF was the average of individual functions. TFs varied among patients, with coefficients of variation for peak amplitude and frequency at peak amplitude of 24.9% and 16.9%, respectively. Intrapatient TF variance with altered loading (> 20% variation in peak amplitude) was observed in 28.5% of patients. Despite this, the generalized TF estimated central arterial pressures to < or = 0.2 +/- 3.8 mm Hg error, arterial compliance to 6 +/- 7% accuracy, and augmentation index to within -7% points (30 +/- 45% accuracy). Individual TFs were only marginally superior to the generalized TF for reconstructing central pressures. CONCLUSIONS Central aortic pressures can be accurately estimated from radial tonometry with the use of a generalized TF. The reconstructed waveform can provide arterial compliance estimates but may underestimate the augmentation index because the latter requires greater fidelity reproduction of the wave contour.

Improved Left Ventricular Mechanics From Acute VDD Pacing in Patients With Dilated Cardiomyopathy and Ventricular Conduction Delay

BACKGROUND Ventricular pacing can improve hemodynamics in heart failure patients, but direct effects on left ventricular (LV) function from varying pacing site and atrioventricular (AV) delay remain unknown. We hypothesized that the magnitude and location of basal intraventricular conduction delay critically influences pacing responses and that single-site pacing in the delay-activated region yields similar or better responses to biventricular pacing. METHODS AND RESULTS Aortic and LV pressures were measured in 18 heart failure patients (mean+/-SD: LV ejection fraction, 19+/-7%; LV end-diastolic pressure, 25+/-8 mm Hg; QRS duration, 157+/-36 ms). Data under normal sinus rhythm were compared with ventricular pacing (VDD) at varying sites and AV delays (randomized order). Right ventricular (RV) apical or midseptal pacing had negligible contractile/systolic effects. However, LV free-wall pacing raised dP/dtmax by 23.7+/-19.0% and pulse-pressure by 18.0+/-18.4% (P<0.01). Biventricular pacing yielded less change (+12.8+/-9.3% in dP/dtmax, P<0.05 versus LV). Pressure-volume analysis performed in 11 patients consistently revealed minimal changes with RV pacing but increased stroke work and lower end-systolic volumes with LV pacing. Optimal AV intervals averaged 125+/-49 ms, and within this range, AV delay had less influence on LV function than pacing site. Basal QRS duration positively correlated with %DeltadP/dtmax (P<0.005), but pacing efficacy was not associated with QRS narrowing. Conduction delay pattern generally predicted pacing sites with most effect. CONCLUSIONS VDD pacing acutely enhances contractile function in heart failure patients with intraventricular conduction delay. Single-site pacing at the site of greatest delay achieves similar or greater benefits to biventricular pacing in such patients. These data clarify pacing-effect mechanisms and should help in candidate identification for future studies.

Coupled systolic-ventricular and vascular stiffening with age: Implications for pressure regulation and cardiac reserve in the elderly☆

OBJECTIVES We tested the hypothesis that age-related arterial stiffening is matched by ventricular systolic stiffening, and that both enhance systolic pressure sensitivity to altered cardiac preload. BACKGROUND Arterial rigidity with age likely enhances blood pressure sensitivity to ventricular filling volume shifts. Tandem increases in ventricular systolic stiffness may also occur and could potentially enhance this sensitivity. METHODS Invasive left ventricular pressure-volume relations were measured by conductance catheter in 57 adults aged 19 to 93 years. Patients had normal heart function and no cardiac hypertrophy and were referred for catheterization to evaluate chest pain. Twenty-eight subjects had normal coronary angiography and hemodynamics, and the remaining had either systolic hypertension or coronary artery disease without infarction. Data recorded at rest and during transient preload reduction by inferior vena caval obstruction yielded systolic and diastolic left ventricular chamber and effective arterial stiffness and pulse pressure. RESULTS Left ventricular volumes, ejection fraction and heart rate were unaltered by age, whereas vascular load and stiffening increased (p < 0.008). Arterial stiffening (Ea) was matched by increased ventricular systolic stiffness (Ees): Ees=0.91 x Ea + 0.53, (r=0.50, p < 0.0001), maintaining arterial-heart interaction (Ea/Ees ratio) age-independent. Ventricular systolic and diastolic stiffnesses correlated (r=0.51, p < 0.0001) and increased with age (p < 0.03). Both ventricular and vascular stiffening significantly increased systolic pressure sensitivity to cardiac preload (p < 0.006). CONCLUSIONS Arterial stiffening with age is matched by ventricular systolic stiffening even without hypertrophy. The two effects contribute to elevating systolic pressure sensitivity to altered chamber filling. In addition to recognized baroreflex and autonomic dysfunction with age, combined stiffening could further enhance pressure lability with diuretics and postural shifts in the elderly.

Noninvasive single-beat determination of left ventricular end-systolic elastance in humans

OBJECTIVES The goal of this study was to develop and validate a method to estimate left ventricular end-systolic elastance (E(es)) in humans from noninvasive single-beat parameters. BACKGROUND Left ventricular end-systolic elastance is a major determinant of cardiac systolic function and ventricular-arterial interaction. However, its use in heart failure assessment and management is limited by lack of a simple means to measure it noninvasively. This study presents a new noninvasive method and validates it against invasively measured E(es). METHODS Left ventricular end-systolic elastance was calculated by a modified single-beat method employing systolic (P(s)) and diastolic (P(d)) arm-cuff pressures, echo-Doppler stroke volume (SV), echo-derived ejection fraction (EF) and an estimated normalized ventricular elastance at arterial end-diastole (E(Nd)): E(es(sb)) = [P(d) - (E(Nd(est)) x P(s) x 0.9)[/(E(Nd(est)) x SV). The E(Nd) was estimated from a group-averaged value adjusted for individual contractile/loading effects; E(es(sb)) estimates were compared with invasively measured values in 43 patients with varying cardiovascular disorders, with additional data recorded after inotropic stimulation (n = 18, dobutamine 5 to 10 microg/kg per min). Investigators performing noninvasive analysis were blinded to the invasive results. RESULTS Combined baseline and dobutamine-stimulated E(es) ranged 0.4 to 8.4 mm Hg/ml and was well predicted by E(es(sb)) over the full range: E(es) = 0.86 x E(es(sb)) + 0.40 (r = 0.91, SEE = 0.64, p < 0.00001, n = 72). Absolute change in E(es(sb)) before and after dobutamine also correlated well with invasive measures: E(es(sb)): DeltaE(es) = 0.86 x DeltaE(es(sb)) + 0.67 (r = 0.88, p < 0.00001). Repeated measures of E(es(sb)) over two months in a separate group of patients (n = 7) yielded a coefficient of variation of 20.3 +/- 6%. CONCLUSIONS The E(es) can be reliably estimated from simple noninvasive measurements. This approach should broaden the clinical applicability of this useful parameter for assessing systolic function, therapeutic response and ventricular-arterial interaction.

Validation of Carotid Artery Tonometry as a Means of Estimating Augmentation Index of Ascending Aortic Pressure

Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both AIs from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies.

Parametric model derivation of transfer function for noninvasive estimation of aortic pressure by radial tonometry

Aortic pressure can be estimated noninvasively by applying a transfer function (TF) to radial tonometry signals. This study compares the performance of prior approaches, based on Fourier transform and inverted aortic-to-radial model, with direct radial-to-aortic autoregressive exogenous (ARX) model. Simultaneous invasive aortic pressure and radial tonometry pressure were recorded during rest in 39 patients in the supine position. Individual radial-aortic TFs were estimated from 20 patients, and the average TF was used to predict aortic pressures in the remaining 19 patients. The direct average TF yielded accurate aortic systolic pressure estimation (error 0.4/spl plusmn/2.9 mmHg) and good reproduction of the aortic pressure waveform (root mean squared error 2.2/spl plusmn/0.9 mmHg). The inverted reverse TF (aortic radial) yielded comparable results, while the Fourier-based TF had worse performance. Individual direct TF provided improved predictive accuracy only for indexes which are based on higher frequency components of the waveform (augmentation index, systolic time period). An ARX average TF can be used to accurately estimate central aortic pressure waveform parameters from noninvasive radial pulse tracings, and its performance is superior to previous techniques.

Quantitation of basal dyssynchrony and acute resynchronization from left or biventricular pacing by novel echo-contrast variability imaging.

OBJECTIVES This study sought to test a novel echocardiographic method based on contrast variability imaging (CVI), to quantify cardiac dyssynchrony and magnitude of resynchronization achieved by left ventricular (LV) and biventricular (BiV) pacing therapy. BACKGROUND Left ventricular or BiV pacing is a promising new therapy for patients with heart failure and intraventricular conduction delay. However, precise quantitation of the extent of resynchronization achieved remains scant. METHODS Ten patients treated with BiV or LV pacing therapy were studied. Echo-contrast was infused slowly, and gated images were acquired before and during contrast appearance. The temporally normalized variance derived from 30 to 50 sequential beats was determined at each pixel to yield the CVI image-displaying improved wall delineation. Systolic regional fractional area of radial sectors was calculated with active and temporarily suspended (AAI) pacing. All analyses were performed blinded to both patient and treatment. RESULTS Pacing increased septal inward motion from -20.4 +/- 9.6% to -30.5 +/- 14.0%, whereas lateral wall motion occurred earlier with no net magnitude change. Both spatial and temporal dyssynchrony in the LV declined nearly 40% with LV or BiV pacing (p < or = 0.001), and this correlated with increasing ejection fraction (31% to 39%; p < 0.02; p < 0.004 for correlation with dyssynchrony). CONCLUSIONS The new imaging and regional dyssynchrony analysis methods provide quantitative assessment of resynchronization analogous to that previously obtained only by tagged magnetic resonance imaging. This could provide a useful noninvasive method for both identifying candidates and following long-term therapy.

Verapamil acutely reduces ventricular-vascular stiffening and improves aerobic exercise performance in elderly individuals

OBJECTIVES We tested the hypothesis that acute intravenous verapamil acutely enhances aerobic exercise performance in healthy older individuals in association with a combined reduction of ventricular systolic and arterial vascular stiffnesses. BACKGROUND Age-related vascular stiffening coupled with systolic ventricular stiffening may limit cardiovascular reserve and, thus, exercise performance in aged individuals. METHODS Nineteen healthy volunteers with mean age 70 +/- 10 years underwent maximal-effort upright ergometry tests on two separate days after receiving either 0.15 mg/kg i.v. verapamil or 0.5 N saline in a double-blind, randomized, crossover study. RESULTS Baseline vascular stiffness, indexed by arterial pulse-wave velocity (Doppler) and augmentation index (carotid tonometry) declined with verapamil (-5.9 +/- 2.1% and -31.7 +/- 12.8%, respectively, both p < 0.05). Preload-adjusted maximal ventricular power, a surrogate for ventricular end-systolic stiffness, also declined by -9.5 +/- 3.6%. Peripheral resistance and peak filling rate were unchanged. With verapamil, exercise duration prior to the anaerobic threshold (AT) increased by nearly 50% (260 +/- 129 to 387 +/- 176 s) with a corresponding 13.4 +/- 4.7% rise in oxygen consumption (VO2) at that time (both p < 0.01). Total exercise duration prolonged by +6 +/- 2.7% (p < 0.05) with no change in maximal VO2. Baseline cardiodepression from verapamil reversed by peak exercise with net increases in stroke volume and cardiac output (p < 0.05). CONCLUSIONS Acute intravenous verapamil reduces ventriculovascular stiffening and improves aerobic exercise performance in healthy aged individuals. This highlights a role for heart-arterial coupling in modulating exertional capacity in the elderly, suggesting a potentially therapeutic target for aged individuals with exertional limitations.

Comparison of Continuous Left Ventricular Volumes by Transthoracic Two-Dimensional Digital Echo Quantification with Simultaneous Conductance Catheter Measurements in Patients with Cardiac Diseases☆

Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 +/- 15 years, range 22 to 70; ejection fraction 63 +/- 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter = slope. DEQ + intercept, slope = 0.94 +/- 0.09, intercept = 5 +/- 8 ml, r2 = 0.86 +/- 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 +/- 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. End-diastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 +/- 0.31, mean intercept 14 +/- 37 ml, average r2 = 0.89 +/- 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 +/- 0.43, intercept = -20 +/- 26 ml, r2 = 0.67 +/- 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans.

Assessment of left ventricular end-systolic elastance from aortic pressure-left ventricular volume relations.

Abstract The left ventricular (LV) end-systolic pressure–volume relation (ESPVR) is a load-insensitive method for evaluating LV contractility, which needs invasive measurement. Some noninvasive methods substitute peak aortic pressure (PS) for end-systolic LV pressure by assuming there is no difference between these pressures. However, this assumption has not been directly validated. With conductance catheter and dual micromanometers, ESPVRs and the slope (EesLV) were constructed from simultaneous LV pressures (LVP) and volumes, aortic pressures (AOP) and LV volumes (EesAO), and PS and LV end-ejection volumes (VEE) (EesPP-EEV) during preload reduction in 50 subjects. The ratio of steady-state PS over VEE (PS/VEE) was also checked. AOP and LVP displayed differences of 11 ± 6 and −30 ± 12 mmHg at the onset and end-ejection, respectively, and −2 ± 4 mmHg at end-systole. EesAO and EesLV were nearly identical: EesAO = 0.97 ×EesLV + 0.05, r2 = 0.99. EesPP-EEV correlated with EesLV (EesPP-EEV = 0.57 ×EesLV + 0.61, r2 = 0.46) but with much more scatter. PS/VEE correlated worst with EesLV. Central AOP can be substituted for LVP to derive EesLV. Other estimation methods yield weaker and poor correlations to directly measured Ees.