Value and Variability of Pulse Shape Indicator for Estimating Mean Arterial Pressure in the Radial and Femoral Arteries.

BACKGROUND: The form factor (FF) is a pulse shape indicator that corresponds to the fraction of pulse pressure added to diastolic blood pressure to estimate the time-averaged mean arterial pressure (MAP). Our invasive study assessed the FF value and variability at the radial and femoral artery levels and evaluated the recommended fixed FF value of 0.33. METHODS AND RESULTS: Hemodynamically stable patients were prospectively included in 2 intensive care units. FF was documented at baseline and during dynamic maneuvers. A total of 632 patients (64±16 years of age, 66% men, MAP=81±14 mm Hg) were included. Among them, 355 (56%) had a radial catheter and 277 (44%) had a femoral catheter. The FF was 0.34±0.06. In multiple linear regression, FF was influenced by biological sex (P<0.0001) and heart rate (P=0.04) but not by height, weight, or catheter location. The radial FF was 0.35±0.06, whereas the femoral FF was 0.34±0.05 (P=0.08). Both radial and femoral FF were higher in women than in men (P<0.05). When using the 0.33 FF value to estimate MAP, the error was -0.4±4.0 mm Hg and -0.1±2.9 mm Hg at the radial and femoral level, respectively, and the MAP estimate still demonstrated high accuracy and good precision even after changes in norepinephrine dose, increase in positive end-expiratory pressure level, fluid administration, or prone positioning (n=218). CONCLUSIONS: Despite higher FF in women and despite interindividual variability in FF, using a fixed FF value of 0.33 yielded accurate and precise estimations of MAP. This finding has potential implications for blood pressure monitoring devices and the study of pulse wave amplification.

Non-Invasive Estimation of Central Systolic Blood Pressure by Radial Tonometry: A Simplified Approach.

BACKROUND: Central systolic blood pressure (cSBP) provides valuable clinical and physiological information. A recent invasive study showed that cSBP can be reliably estimated from mean (MBP) and diastolic (DBP) blood pressure. In this non-invasive study, we compared cSBP calculated using a Direct Central Blood Pressure estimation (DCBP = MBP2/DBP) with cSBP estimated by radial tonometry. METHODS: Consecutive patients referred for cardiovascular assessment and prevention were prospectively included. Using applanation tonometry with SphygmoCor device, cSBP was estimated using an inbuilt generalized transfer function derived from radial pressure waveform, which was calibrated to oscillometric brachial SBP and DBP. The time-averaged MBP was calculated from the radial pulse waveform. The minimum acceptable error (DCBP-cSBP) was set at ≤5 (mean) and ≤8 mmHg (SD). RESULTS: We included 160 patients (58 years, 54%men). The cSBP was 123.1 ± 18.3 mmHg (range 86-181 mmHg). The (DCBP-cSBP) error was -1.4 ± 4.9 mmHg. There was a linear relationship between cSBP and DCBP (R2 = 0.93). Forty-seven patients (29%) had cSBP values ≥ 130 mmHg, and a DCBP value > 126 mmHg exhibited a sensitivity of 91.5% and specificity of 94.7% in discriminating this threshold (Youden index = 0.86; AUC = 0.965). CONCLUSIONS: Using the DCBP formula, radial tonometry allows for the robust estimation of cSBP without the need for a generalized transfer function. This finding may have implications for risk stratification.

Pulsatile pulmonary artery pressure in a large animal model of chronic thromboembolic pulmonary hypertension: Similarities and differences with human data.

A striking feature of the human pulmonary circulation is that mean (mPAP) and systolic (sPAP) pulmonary artery pressures (PAPs) are strongly related and, thus, are essentially redundant. According to the empirical formula documented under normotensive and hypertensive conditions (mPAP = 0.61 sPAP + 2 mmHg), sPAP matches ~160%mPAP on average. This attests to the high pulsatility of PAP, as also witnessed by the near equality of PA pulse pressure and mPAP. Our prospective study tested if pressure redundancy and high pulsatility also apply in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). At baseline (Week-0, W0), Sham (n = 8) and CTEPH (n = 27) had similar mPAP and stroke volume. At W6, mPAP increased in CTEPH only, with a two- to three-fold increase in PA stiffness and total pulmonary resistance. Seven CTEPH piglets were also studied at W16 at baseline, after volume loading, and after acute pulmonary embolism associated with dobutamine infusion. There was a strong linear relationship between sPAP and mPAP (1) at W0 and W6 (n = 70 data points, r² = 0.95); (2) in the subgroup studied at W16 (n = 21, r² = 0.97); and (3) when all data were pooled (n = 91, r² = 0.97, sPAP range 9-112 mmHg). The PA pulsatility was lower than that expected based on observations in humans: sPAP matched ~120%mPAP only and PA pulse pressure was markedly lower than mPAP. In conclusion, the redundancy between mPAP and sPAP seems a characteristic of the pulmonary circulation independent of the species. However, it is suggested that the sPAP thresholds used to define PH in animals are species- and/or model-dependent and thus must be validated.

Arterial and Cardiac Remodeling Associated With Extra Weight Gain in an Isolated Abdominal Obesity Cohort.

Introduction: This study aims to assess the changes in cardiovascular remodeling attributable to bodyweight gain in a middle-aged abdominal obesity cohort. A remodeling worsening might explain the increase in cardiovascular risk associated with a dynamic of weight gain. Methods: Seventy-five middle-aged subjects (56 ± 5 years, 38 women) with abdominal obesity and no known cardiovascular disease underwent MRI-based examinations at baseline and at a 6.1 ± 1.2-year follow-up to monitor cardiovascular remodeling and hemodynamic variables, most notably the effective arterial elastance (Ea). Ea is a proxy of the arterial load that must be overcome during left ventricular (LV) ejection, with increased EA resulting in concentric LV remodeling. Results: Sixteen obese subjects had significant weight gain (>7%) during follow-up (WG+), whereas the 59 other individuals did not (WG-). WG+ and WG- exhibited significant differences in the baseline to follow-up evolutions of several hemodynamic parameters, notably diastolic and mean blood pressures (for mean blood pressure, WG+: +9.3 ± 10.9 mmHg vs. WG-: +1.7 ± 11.8 mmHg, p = 0.022), heart rate (WG+: +0.6 ± 9.4 min-1 vs. -8.9 ± 11.5 min-1, p = 0.003), LV concentric remodeling index (WG: +0.08 ± 0.16 g.mL-1 vs. WG-: -0.02 ± 0.13 g.mL-1, p = 0.018) and Ea (WG+: +0.20 ± 0.28 mL mmHg-1 vs. WG-: +0.01 ± 0.30 mL mmHg-1, p = 0.021). The evolution of the LV concentric remodeling index and Ea were also strongly correlated in the overall obese population (p < 0.001, R2 = 0.31). Conclusions: A weight gain dynamic is accompanied by increases in arterial load and load-related concentric LV remodeling in an isolated abdominal obesity cohort. This remodeling could have a significant impact on cardiovascular risk.

The isobaric pulmonary arterial compliance in pulmonary hypertension.

Pulmonary hypertension is associated with stiffening of pulmonary arteries which increases right ventricular pulsatile loading. High pulmonary artery wedge pressure (PAWP) in postcapillary pulmonary hypertension (Pc-PH) further decreases pulmonary arterial compliance (PAC) at a given pulmonary vascular resistance (PVR) compared with precapillary pulmonary hypertension, thus responsible for a higher total arterial load. In all other vascular beds, arterial compliance is considered as mainly determined by the distending pressure, due to non-linear stress-strain behaviour of arteries. We tested the applicability, advantages and drawbacks of two comparison methods of PAC depending on the level of mean pulmonary arterial pressure (mPAP; isobaric PAC) or PVR. Right heart catheterisation data including PAC (stroke volume/pulse pressure) were obtained in 112 Pc-PH (of whom 61 had combined postcapillary and precapillary pulmonary hypertension) and 719 idiopathic pulmonary arterial hypertension (iPAH). PAC could be compared over the same mPAP range (25-66 mmHg) in 792 (95.3%) out of 831 patients and over the same PVR range (3-10.7 WU) in only 520 (62.6%) out of 831 patients. The main assumption underlying comparisons at a given PVR was not verified as the PVR×PAC product (RC-time) was not constant but on the contrary more variable than mPAP. In the 788/831 (94.8%) patients studied over the same PAC range (0.62-6.5 mL·mmHg-1), PVR and thus total arterial load tended to be higher in iPAH. Our study favours comparing PAC at fixed mPAP level (isobaric PAC) rather than at fixed PVR. A reappraisal of the effects of PAWP on the pulsatile and total arterial load put on the right heart is needed, and this point deserves further studies.

Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

BACKGROUND: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population. METHODS: Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. RESULTS: 55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP levels. All subjects accepted RHC at inclusion, which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension (21.8%). At long-term follow-up (118.8 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up. CONCLUSIONS: Asymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH.

New Method to Estimate Central Systolic Blood Pressure From Peripheral Pressure: A Proof of Concept and Validation Study.

Objective: The non-invasive estimation of central systolic blood pressure (cSBP) is increasingly performed using new devices based on various pulse acquisition techniques and mathematical analyses. These devices are most often calibrated assuming that mean (MBP) and diastolic (DBP) BP are essentially unchanged when pressure wave travels from aorta to peripheral artery, an assumption which is evidence-based. We tested a new empirical formula for the direct central blood pressure estimation of cSBP using MBP and DBP only (DCBP = MBP2/DBP). Methods and Results: First, we performed a post-hoc analysis of our prospective invasive high-fidelity aortic pressure database (n = 139, age 49 ± 12 years, 78% men). The cSBP was 146.0 ± 31.1 mmHg. The error between aortic DCBP and cSBP was -0.9 ± 7.4 mmHg, and there was no bias across the cSBP range (82.5-204.0 mmHg). Second, we analyzed 64 patients from two studies of the literature in whom invasive high-fidelity pressures were simultaneously obtained in the aorta and brachial artery. The weighed mean error between brachial DCBP and cSBP was 1.1 mmHg. Finally, 30 intensive care unit patients equipped with fluid-filled catheter in the radial artery were prospectively studied. The cSBP (115.7 ± 18.2 mmHg) was estimated by carotid tonometry. The error between radial DCBP and cSBP was -0.4 ± 5.8 mmHg, and there was no bias across the range. Conclusion: Our study shows that cSBP could be reliably estimated from MBP and DBP only, provided BP measurement errors are minimized. DCBP may have implications for assessing cardiovascular risk associated with cSBP on large BP databases, a point that deserves further studies.

A systematic review of invasive, high-fidelity pressure studies documenting the amplification of blood pressure from the aorta to the brachial and radial arteries.

It is commonly accepted that systolic blood pressure (SBP) is significantly higher in the brachial/radial artery than in the aorta while mean (MBP) and diastolic (DBP) pressures remain unchanged. This may have implications for outcome studies and for non-invasive devices calibration. We performed a systematic review of invasive high-fidelity pressure studies documenting BP in the aorta and brachial/radial artery. We selected articles published prior to July 2015. Pressure amplification (Amp = peripheral minus central pressure) was calculated (weighted mean). The six studies retained (n = 294, 76.5% male, mean age 63.5 years) mainly involved patients with suspected coronary artery disease (CAD). In two studies at the aortic/brachial level (n = 64), MBP and DBP were unchanged (MPAmp = 0.1 mmHg, DPAmp = -1.3 mmHg), while SBP increased (SPAmp = 4.2 mmHg; relative amplification = 3.1%). In four studies in which MBP was not documented (n = 230), brachial DBP remained unchanged and SBP increased (SPAmp = 6.6 mmHg; 4.9%). One of these four studies also reported radial SBP and DBP, not MBP (n = 12). Few high-fidelity pressure studies were found, and they have been performed mainly in elderly male patients with suspected CAD. Counter to expectations, the mean amplification of SBP from the aorta to brachial artery was < 5%. Further studies on SPAmp phenotypes (positive, null, negative) are advocated. Non-invasive device calibration assumptions were confirmed, namely unchanged MBP and DBP from the aorta to the brachial artery. Data did not allow for firm conclusions on the amount of BP changes from the aorta to the radial artery, and from the aorta to the brachial/radial arteries in other populations.

Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension.

Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans. Angiophagy was defined by pathological assessment as the moving of an embolic specimen from the lumen to the interstitium according to three stages in a pig model of chronic thromboembolic pulmonary hypertension (CTEPH) 6 to 10 weeks after embolization with enbucrilate: the embolic specimen is (I) covered by endothelial cells, (II) covered by endothelial cells and smooth muscle cells, and (III) located in the adventitia. In animals, we observed the three stages of the pulmonary angiophagy of enbucrilate emboli in <300 µm PA. Stages II and III were observed in 300 to 1000 µm PA, and only Stage I was observed in larger-diameter PA (>1000 µm). In lung samples from patients with histories of pulmonary embolisms, we observed PA angiophagy stigma for embolic specimens derived from blood clots and from bone marrow emboli. This study provides an original pathological description and staging of PA angiophagy in a large animal model of CTEPH and in humans after pulmonary embolism.

Volume Infusion Markedly Increases Femoral dP/dtmax in Fluid-Responsive Patients Only.

OBJECTIVES: To evaluate the preload dependence of femoral maximal change in pressure over time (dP/dtmax) during volume expansion in preload dependent and independent critically ill patients. DESIGN: Retrospective database analysis. SETTING: Two adult polyvalent ICUs. PATIENTS: Twenty-five critically ill patients with acute circulatory failure. INTERVENTIONS: Thirty-five fluid infusions of 500 mL normal saline. MEASUREMENTS AND MAIN RESULTS: Changes in femoral dP/dtmax, systolic, diastolic, and pulse femoral arterial pressure were obtained from the pressure waveform analysis using the PiCCO2 system (Pulsion Medical Systems, Feldkirchen, Germany). Stroke volume index was obtained by transpulmonary thermodilution. Statistical analysis was performed comparing results before and after volume expansion and according to the presence or absence of preload dependence (increases in stroke volume index ≥ 15%). Femoral dP/dtmax increased by 46% after fluid infusion in preload-dependent cases (mean change = 510.6 mm Hg·s; p = 0.005) and remained stable in preload-independent ones (mean change = 49.2 mm Hg·s; p = 0.114). Fluid-induced changes in femoral dP/dtmax correlated with fluid-induced changes in stroke volume index in preload-dependent cases (r = 0.618; p = 0.032), but not in preload-independent ones. Femoral dP/dtmax strongly correlated with pulse and systolic arterial pressures and with total arterial stiffness, regardless of the preload dependence status (r > 0.9 and p < 0.001 in all cases). CONCLUSIONS: Femoral dP/dtmax increased with volume expansion in case of preload dependence but not in case of preload independence and was strongly related to pulse pressure and total arterial stiffness regardless of preload dependence status. Therefore, femoral dP/dtmax is not a load-independent marker of left ventricular contractility and should be not used to track contractility in critically ill patients.

Echocardiographic Evaluation of Left Ventricular Filling Pressure in Patients With Heart Failure With Preserved Ejection Fraction: Usefulness of Inferior Vena Cava Measurements and 2016 EACVI/ASE Recommendations.

CONTEXT: The left ventricular filling pressure (LVFP) is correlated to right atrial pressure (RAP) in heart failure. We compared diagnostic value of the inferior vena cava (IVC) measurements to the one of the 2016 echocardiographic recommendations to estimate LVFP in patients with suspected heart failure with preserved ejection fraction (HFpEF). METHODS: Invasive hemodynamics and echocardiography were obtained within 48 hours in 132 consecutive patients with left ventricular ejection fraction ≥50%, and suspected pulmonary hypertension. Increased LVFP was defined by a pulmonary artery wedge pressure (PAWP) >15 mmHg. RESULTS: Of 83 patients in sinus rhythm, a score of the 2016 recommendations ≥ 2 (E/e' ratio >14 and/or tricuspid regurgitation velocity >2.8 m/s and/or indexed left atrial volume>34 mL /m²) had a positive predictive value (PPV) of 63% for PAWP>15 mmHg, whereas a dilated IVC (>2.1 cm) and/or non-collapsible (≤50%) had a PPV of 82%. The net reclassification improvement was 0.39 (P < .05). In atrial fibrillation (AF), a dilated and/or non-collapsible IVC had an 86% PPV for PAWP>15 mmHg. The correlation between RAP and PAWP was 0.60, with 75.7% concordance (100/132) between dichotomized pressures (both RAP>8 mmHg and PAWP>15 mmHg and vice versa). CONCLUSION: The IVC size and collapsibility is valuable to identify patients with HFpEF with high LVFP in both sinus rhythm and AF.

Influence of changes in ventricular systolic function and loading conditions on pulse contour analysis-derived femoral dP/dtmax.

BACKGROUND: Femoral dP/dtmax (maximum rate of the arterial pressure increase during systole) measured by pulse contour analysis has been proposed as a surrogate of left ventricular (LV) dP/dtmax and as an estimator of LV systolic function. However, femoral dP/dtmax may be influenced by LV loading conditions. In this study, we evaluated the impact of variations of LV systolic function, preload and afterload on femoral dP/dtmax in critically ill patients with cardiovascular failure to ascertain its reliability as a marker of LV systolic function. RESULTS: We performed a prospective observational study to evaluate changes in femoral dP/dtmax, thermodilution-derived variables (PiCCO2-Pulsion Medical Systems, Feldkirchen, Germany) and LV ejection fraction (LVEF) measured by transthoracic echocardiography during variations in dobutamine and norepinephrine doses and during volume expansion (VE) and passive leg raising (PLR). Correlations with arterial pulse and systolic pressure, effective arterial elastance, total arterial compliance and LVEF were also evaluated. In absolute values, femoral dP/dtmax deviated from baseline by 21% (201 ± 297 mmHg/s; p = 0.013) following variations in dobutamine dose (n = 17) and by 15% (177 ± 135 mmHg/s; p < 0.001) following norepinephrine dose changes (n = 29). Femoral dP/dtmax remained unchanged after VE and PLR (n = 24). Changes in femoral dP/dtmax were strongly correlated with changes in pulse pressure and systolic arterial pressure during dobutamine dose changes (R = 0.942 and 0.897, respectively), norepinephrine changes (R = 0.977 and 0.941, respectively) and VE or PLR (R = 0.924 and 0.897, respectively) (p < 0.05 in all cases). Changes in femoral dP/dtmax were correlated with changes in LVEF (R = 0.527) during dobutamine dose variations but also with effective arterial elastance and total arterial compliance in the norepinephrine group (R = 0.638 and R = - 0.689) (p < 0.05 in all cases). CONCLUSIONS: Pulse contour analysis-derived femoral dP/dtmax was not only influenced by LV systolic function but also and prominently by LV afterload and arterial waveform characteristics in patients with acute cardiovascular failure. These results suggest that femoral dP/dtmax calculated by pulse contour analysis is an unreliable estimate of LV systolic function during changes in LV afterload and arterial load by norepinephrine and directly linked to arterial waveform determinants.