Antoine Guilcher

Peripheral Augmentation Index Defines the Relationship Between Central and Peripheral Pulse Pressure

Peripheral systolic blood pressure is amplified above central aortic systolic pressure, but the late systolic shoulder of the peripheral pulse may approximate central systolic pressure. Because late systolic pressure also determines the peripheral augmentation index, a measure of pressure wave reflection within the systemic circulation, this implies a direct relationship between amplification and augmentation. We compared the late systolic shoulder of the peripheral pressure waveform with estimates of central systolic pressure obtained using a transfer function in 391 subjects undergoing diagnostic coronary angiography and/or elective angioplasty (30% with insignificant coronary artery disease). In a subset (n=12) we compared the late systolic shoulder of the peripheral pulse with central pressure obtained with a catheter placed in the aortic root. Measurements were made at baseline, during atrial pacing, and during administration of nitroglycerin. Late systolic shoulder pressure closely approximated transfer function estimates of central pressure (R=0.96; P<0.0001; mean difference±SD: 0.5±5.2 mm Hg). Despite changes in waveform morphology induced by pacing and nitroglycerin (reducing mean values±SE of the augmentation index from 76±3.8% to 66±4.6% and 60±3.3%, respectively), there was close agreement between the late systolic shoulder of the peripheral pulse and measured values of central pressure (R=0.96; P<0.001; mean difference: 1.7±4.8 mm Hg). In conclusion, the late systolic shoulder of the peripheral pulse closely approximates central systolic pressure and peripheral augmentation index, the ratio of central:peripheral pulse pressure. Interventions to lower augmentation index and peripheral vascular resistance will have multiplicative effects in lowering central blood pressure.

Exercise reduces arterial pressure augmentation through vasodilation of muscular arteries in humans

Exercise markedly influences pulse wave morphology, but the mechanism is unknown. We investigated whether effects of exercise on the arterial pulse result from alterations in stroke volume or pulse wave velocity (PWV)/large artery stiffness or reduction of pressure wave reflection. Healthy subjects (n = 25) performed bicycle ergometry. with workload increasing from 25 to 150 W for 12 min. Digital arterial pressure waveforms were recorded using a servo-controlled finger cuff. Radial arterial pressure waveforms and carotid-femoral PWV were determined by applanation tonometry. Stroke volume was measured by echocardiography, and brachial and femoral artery blood flows and diameters were measured by ultrasound. Digital waveforms were recorded continuously. Other measurements were made before and after exercise. Exercise markedly reduced late systolic and diastolic augmentation of the peripheral pressure pulse. At 15 min into recovery, stroke volume and PWV were similar to baseline values, but changes in pulse wave morphology persisted. Late systolic augmentation index (radial pulse) was reduced from 54 +/- 3.9% at baseline to 42 +/- 3.7% (P < 0.01), and diastolic augmentation index (radial pulse) was reduced from 37 +/- 1.8% to 25 +/- 2.9% (P < 0.001). These changes were accompanied by an increase in femoral blood flow (from 409 +/- 44 to 773 +/- 48 ml/min, P < 0.05) and an increase in femoral artery diameter (from 8.2 +/- 0.4 to 8.6 +/- 0.4 mm, P < 0.05). In conclusion, exercise dilates muscular arteries and reduces arterial pressure augmentation, an effect that will enhance ventricular-vascular coupling and reduce load on the left ventricle.

Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon

Background— The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. Methods and Results— Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (P<0.01). A 33% decline in aortic pressure augmentation in Ex2 (P<0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (P<0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P<0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (P<0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. Conclusions— On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular–ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.

Augmentation pressure is influenced by ventricular contractility/relaxation dynamics: novel mechanism of reduction of pulse pressure by nitrates.

Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 &mgr;g sublingually, n=20) and locally by intracoronary infusion (1 &mgr;g/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg (P<0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each P<0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced (P<0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg (P<0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation.Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 μg sublingually, n=20) and locally by intracoronary infusion (1 μg/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg ( P <0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each P <0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced ( P <0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg ( P <0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation. # Novelty and Significance {#article-title-30}

Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation DynamicsNovelty and Significance: Novel Mechanism of Reduction of Pulse Pressure by Nitrates

Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 &mgr;g sublingually, n=20) and locally by intracoronary infusion (1 &mgr;g/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg (P<0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each P<0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced (P<0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg (P<0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation.Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 μg sublingually, n=20) and locally by intracoronary infusion (1 μg/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg ( P <0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each P <0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced ( P <0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg ( P <0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation. # Novelty and Significance {#article-title-30}

Coronary Wave Energy A Novel Predictor of Functional Recovery After Myocardial Infarction

Background—Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Methods and Results—Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=–0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m–2 s–2×105 predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=–0.34; P=0.07). Conclusions—The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

Dominance of the Forward Compression Wave in Determining Pulsatile Components of Blood Pressure: Similarities Between Inotropic Stimulation and Essential Hypertension

Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.8±11.3 years; 165±26.6/99±14.2 mm Hg) and normotensive subjects (52.2±12.6 years; 120±14.2/71±8.2 mm Hg). Dobutamine (7.5 &mgr;g/kg per minute) increased the forward compression wave generated by the ventricle and increased pulse pressure from 36.8±3.7 to 59.0±3.4 mm Hg (mean±SE) but had no significant effect on mean arterial pressure or the midsystolic backward compression wave. By contrast, norepinephrine (50 ng/kg per minute) had no significant effect on the forward compression wave but increased the midsystolic backward compression wave. Despite this increase in the backward compression wave, and an increase in mean arterial pressure, norepinephrine increased central pulse pressure less than dobutamine (increases of 22.1±3.8 and 7.2±2.8 mm Hg for dobutamine and norepinephrine, respectively; P<0.02). An elevated forward wave component (mean±SE, 50.4±3.4 versus 35.2±1.8 mm Hg, in hypertensive and normotensive subjects, respectively; P<0.001) accounted for approximately two thirds of the total difference in central pulse pressures between hypertensive and normotensive subjects. Increased central pulse pressure during inotropic stimulation and in essential hypertension results primarily from the forward compression wave.Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.8±11.3 years; 165±26.6/99±14.2 mm Hg) and normotensive subjects (52.2±12.6 years; 120±14.2/71±8.2 mm Hg). Dobutamine (7.5 μg/kg per minute) increased the forward compression wave generated by the ventricle and increased pulse pressure from 36.8±3.7 to 59.0±3.4 mm Hg (mean±SE) but had no significant effect on mean arterial pressure or the midsystolic backward compression wave. By contrast, norepinephrine (50 ng/kg per minute) had no significant effect on the forward compression wave but increased the midsystolic backward compression wave. Despite this increase in the backward compression wave, and an increase in mean arterial pressure, norepinephrine increased central pulse pressure less than dobutamine (increases of 22.1±3.8 and 7.2±2.8 mm Hg for dobutamine and norepinephrine, respectively; P <0.02). An elevated forward wave component (mean±SE, 50.4±3.4 versus 35.2±1.8 mm Hg, in hypertensive and normotensive subjects, respectively; P <0.001) accounted for approximately two thirds of the total difference in central pulse pressures between hypertensive and normotensive subjects. Increased central pulse pressure during inotropic stimulation and in essential hypertension results primarily from the forward compression wave. # Novelty and Significance {#article-title-19}

Estimating central Sbp from the peripheral pulse: influence of waveform analysis and calibration error

Objective To compare estimation of central cSBP by application of a generalized transfer function (GTF) to a peripheral arterial waveform and from the late systolic shoulder (SBP2) of such a waveform and assess errors introduced by noninvasive calibration of the waveform. Methods The digital arterial pulse was acquired noninvasively with a servo-controlled finger cuff. A high fidelity pressure tipped catheter was placed in the proximal aortic root. Measurements were made at baseline (n = 40), after nitrovasodilation, handgrip exercise (n = 18) and during pacing (n = 10). Estimates of cSBP obtained using a GTF and from SBP2 (using an algorithm applied to individual cardiac cycles) of the digital arterial waveform were compared with values measured at the aortic root. Results When arterial waveforms were calibrated from aortic intra-arterial mean and DBP there was close agreement between estimated and measured cSBP: mean difference between estimated and measured cSBP (SD): 1.0 (5.7) and −0.7 (5.5) mmHg for GTF and SBP2, respectively. Noninvasive oscillometric calibration increased variability in estimation of cSBP [mean difference, 1.3 (11) mmHg for SBP2] but estimates of the cSBP to peripheral systolic pressure increment from oscillometric calibration of SBP2 agreed well with those obtained using invasive calibration [mean difference −2.4 (6.1) mmHg]. Conclusion SBP2 potentially provides a simple measure of cSBP and is of comparable accuracy to a GTF. Noninvasive calibration increases variability for both methods but has less effect on the cSBP to peripheral SBP increment.

Estimating central systolic blood pressure during oscillometric determination of blood pressure: proof of concept and validation by comparison with intra-aortic pressure recording and arterial tonometry.

ObjectivesCentral systolic blood pressure is usually estimated by transformation of a peripheral arterial waveform obtained by tonometry and calibrated from conventional measurements of brachial artery blood pressure from a brachial cuff using the oscillometric principle. We investigated whether central blood pressure could be obtained directly from a brachial cuff waveform, allowing the measurement of central blood pressure to be incorporated into the standard oscillometric determination of blood pressure. MethodsValues of central systolic blood pressure obtained from a brachial cuff waveform were compared with those obtained using a pressure-tipped intra-aortic catheter in 29 individuals undergoing cardiac catheterization. To remove errors introduced by the measurement of peripheral blood pressure, transformed brachial waveforms were calibrated using values of mean and diastolic pressure from the intra-aortic catheter. In a second study, the values obtained from the brachial cuff were compared with those obtained using a noninvasive tonometric method using calibration from mean and diastolic and from systolic and diastolic blood pressure derived from a standard oscillometric algorithm in 100 individuals (46 women, 19–81 years) with blood pressure ranging from 89/52 to 230/117 mmHg. ResultsIn study 1, the mean difference±SD of brachial cuff-derived values and intra-aortic values was 0.0±5.9 mmHg. In study 2, the mean difference for brachial cuff-derived values and tonometer values was −0.6±3.9 and 1.6±4.5 mmHg when calibrated using brachial mean and diastolic and brachial systolic and diastolic pressures, respectively. ConclusionCentral systolic blood pressure can be obtained from a brachial cuff waveform with an accuracy comparable to that of a tonometer.

The noninvasive estimation of central aortic blood pressure in patients with aortic stenosis

Objectives To determine the relationship between brachial blood pressure, and transfer function-estimated and invasively measured central aortic pressure in patients with at least moderate symptomatic aortic stenosis. Methods Fourteen patients aged 54–81 years with mean (SD) effective valve area of 0.69 (0.20) cm2, undergoing coronary angiography, had simultaneous peripheral and central aortic blood pressure measurements. Brachial blood pressure was determined by an oscillometric method. Aortic pressure was measured directly using pressure transducer tipped catheters, and estimated indirectly by the application of a transfer function to a radial arterial waveform obtained by tonometry. Results Measured aortic systolic pressure did not differ significantly from brachial pressure [mean difference (SD) 2 (9) mmHg, P = not significant (NS)]. Transfer function estimates of central systolic pressure obtained from the radial waveform calibrated from brachial pressure were less accurate [mean difference −8 (7) mmHg, P = 0.001]. Recalibration of the radial waveforms using the invasive mean and diastolic blood pressure improved the agreement [mean difference −2 (6) mmHg, P = NS] but did not provide a better estimate than brachial blood pressure. The accuracy of noninvasively estimated subendocardial viability ratio was substantially improved by recalibration of radial arterial waveforms using corrected ejection time. Conclusion In patients with aortic stenosis there is clinically acceptable agreement between noninvasive brachial pressure and directly measured central aortic pressure.