| Background and ObjectiveThe intracardiac pressures are the core parameters of cardiac function evaluation.The gold standard for intracardiac pressures measurement is invasive catheterization with complex procedures and potential complications.There is no alternative noninvasive method for quantitative measurement of the intracardiac pressures,including the left ventricular diastolic pressure(also pulmonary diastolic pressure),right ventricular diastolic pressure(also right atrial pressure)and right ventricular systolic pressure.Ultrasound imaging has been widely used as a powerful tool for the evaluation of cardiac function and cardiovascular disease diagnosis.Although many qualitative or semi-quantitative methods or indices for intracardiac pressure estimations has been developed after those years of study,they can only serve as auxiliary determinations.For now,the invasive intracardiac pressure measurement by catheterization is irreplaceable.The diastolic pressure gradient across the pulmonary valve(PVPG)is an essential component of noninvasive evaluation of pulmonary diastolic pressure.It can provide important information for the prognosis of patients with heart failure and coronary heart disease,pulmonary hypertension diagnosis and classification,and evaluation of left ventricular diastolic function.Among the current noninvasive measurement methods,the pulmonary regurgitation(PR)method is not applicable to more than 1/3 target patients without PR,the tricuspid regurgitation(TR)method is of a wide range of bias,which can compromise clinical diagnosis.The right atrial pressure(RAP)is the cornerstone of noninvasive intracardiac pressure evaluation.It not only can be used as the substitute of right ventricular diastolic pressure,but also is an essential component of noninvasive evaluation of right ventricular systolic pressure(also pulmonary systolic pressure)and pulmonary diastolic pressure.RAP is of great clinical value in assessment of right ventricular volume load and fluid responsiveness,pulmonary hypertension and right ventricular diastolic function.At present,the most widely used methods for noninvasive estimations of RAP in clinic,which depends on the hemodynamic information or diameter changes of right heart or vena cava,is only qualitative or semi-quantitative,and clinicians always need to combine several indices to make judgement.Similar pitfalls exist in the other noninvasive ultrasound methods based on diameter changes of internal jugular vein(IJV)or femoral vein.In addition,there are several methods using water or air balloon to compress the peripheral veins,which are of wide ranges of bias.Also,due to the lack of accurate right atrium location,studies derived from classical physical examination showed poor agreement with invasive measurements.The purpose of present study is to establish new methods for noninvasive quantification of PVPG and RAP,and to testify their usefulness in clinical practice by comparison with invasive pressure measurements.Methods 1.Noninvasive quantification of PVPGOne hundred and two subjects were included(50 males and 52 females),their average age is 39 years old.Quantitative Muller maneuver was performed to induce the pulmonary valve premature opening in diastole.Siemens Acuson Sequoia 512 ultrasound machine was used to observe the flow wave of pulmonary valve using pulse wave Doppler.A customized intrathoracic negative pressure measurement device was used to record the amplitude of Muller maneuver at the moment of pulmonary valve premature opening in diastole as PVPG.Among the 102 subjects,43 subjects underwent invasive right heart catheterization for clinical diagnosis or treatment,the other 59 subjects were measured by echocardiography using PR method.PVPG measured by our new method,catheterization method and PR method were compared to evaluated their correlation and agreement,respectively.Thirteen subjects were selected randomly to test the reproducibility of our new method.2.Noninvasive quantification of RAPSeventy-six subjects were included(46 males and 30 females),their average age is 54 years old.M-Turbo portable ultrasound machine was used to measure RAP noninvasively.By accurate location of the collapse point of IJV and the center of the right atrium using ultrasound imaging,the vertical distance between those 2 points was measured as the noninvasive RAP.Our new method was performed at the right IJV before the surgical operation and at the left IJV after the operation.The central venous catheterization measurement of RAP was done within 15 minutes after the noninvasive measurement by ultrasound,and continuously monitored after operation.RAP measured by our new method and catheterization method were compared to evaluated their correlation and agreement.Fifteen subjects were selected randomly to test the reproducibility of our new method.Results 1.Noninvasive quantification of PVPGIn PR group,mean PVPG measured by our new method and PR method was 9.4 mmHg and 7.2 mmHg,respectively.The new method showed good correlation and agreement with PR method.The correlation coefficient was 0.90(P<0.001),and the Lin coefficient was 0.70(P<0.001)with a 95% confidence interval(CI)of 0.61 to 0.77.Bland-Altman analysis showed the mean difference between PR method and our new method was 2.2 mmHg and the limits of agreement(LOA)was-4.9 mmHg to 9.3 mmHg.In catheterization group,mean PVPG measured by our new method and catheterization method was 13.2 mmHg and 11.5 mmHg,respectively.The new method showed great correlation and agreement with catheterization method.The correlation coefficient was 0.95(P<0.001),and the Lin coefficient was 0.91(P<0.001)with a 95% CI of 0.86 to 0.95.Bland-Altman analysis showed the mean difference between catheterization method and our new method was 1.7 mmHg and LOA was-3.1 mmHg to 6.5 mmHg.A stratified analysis of agreement using 12 mmHg by invasive measurement as the cut-off.In both subgroups,PVPO measures overestimated the pressure gradient,which was more evident in the higher one.There was significant difference of the PVPG errors between subgroups(Low pressure gradient group vs.High pressure gradient group,1.0 mmHg,LOA:-3.5 mmHg to 5.5 mmHg vs.3.1 mmHg,LOA:-0.6 mmHg to 6.9 mmHg).The reproducibility test of 13 randomly selected subject showed good intra-and inter-observer agreement.The intra-class correlation coefficients of intra-observer variability and inter-observer variability were 0.98(95% CI,0.96~0.99)and 0.93(95% CI,0.79~0.98),respectively.Bland-Altman analysis showed the mean difference between measurements taken by the same observer and by two independent observers was-0.3 mmHg(LOA,-1.8 mmHg to 1.2 mmHg)and-0.3 mmHg(LOA,-3.8 mmHg to 3.2 mmHg),respectively.2.Noninvasive quantification of RAPA total of 118 noninvasive measurements by ultrasound were performed(74 preoperative measurements and 44 postoperative measurements).The mean time for noninvasive measurement was about 3 minutes(182±47 s).The preoperative mean RAP measured by our new method and catheterization method was 7.9 mmHg and 8.1 mmHg,respectively.Correlation analysis revealed a highly positive correlation between the two methods(r=0.898,P<0.001),and the Lin coefficient was 0.89(P<0.001)with a 95% CI of 0.83 to 0.93.Bland-Altman analysis showed a mean difference of 0.22 mmHg(95% CI,-0.06 mmHg to 0.50 mmHg),and LOA was-2.16 mmHg to 2.59 mmHg.The postoperative mean RAP measured by our new method and catheterization method was 8.7 mmHg and 8.6 mmHg,respectively.Correlation analysis revealed a highly positive correlation between the two methods(r=0.928,P<0.001),and the Lin coefficient was 0.92(P<0.001)with a 95% CI of 0.87 to 0.96.Bland-Altman analysis showed a mean difference of-0.09 mmHg(95% CI,-0.41 mmHg to 0.22 mmHg),and LOA was-2.12 mmHg to 1.94 mmHg.There were 42 patients who had 2 sets of measurements.Changes of noninvasive RAP were highly correlated with those of invasive measurements(r=0.906,P<0.001;Lin coefficient 0.91,95% CI 0.83 to 0.95,P<0.001).Bland-Altman analysis showed that the mean difference between them was-0.08 mmHg(95% CI,-0.43 to 0.26 mm Hg)with LOA being-2.25 to 2.08 mm Hg.The reproducibility test of 15 randomly selected subject showed good intra-observer agreement.The intra-class correlation coefficient was 0.97(95% CI,0.91 to 0.99).Bland-Altman analysis showed the mean difference between measurements taken by two independent observers was-0.16 mmHg(LOA,-0.60 mmHg to 0.28 mmHg).Conclusions1.The noninvasive quantification of PVPG can be achieved by Muller maneuver induced pulmonary valve premature opening in diastole.The new method is independent of PR or TR.In comparison with invasive measurements,our new method meets the quantification requirement of PVPG in clinic.2.The noninvasive quantification of RAP can be achieved by accurate location of right atrial center and collapse point of IJV using ultrasound imaging,which is simple and quick.In comparison with invasive measurements,our new method successfully quantified RAP noninvasively,may serve as an alternative method of invasive catheterization. |
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