Assessment of the sensitivity of hydrogen inhalation in the detection of left-to-right shunting

For the detection of left-to-right intracardiac shunting, the oximetric and standard indocyanine green techniques are relatively insensitive, in that neither can reliably detect a shunt with a ratio of pulmonary to systemic flow (Qp/Qs) less than 1.3 (percentage shunt, 23%). Although the hydrogen inhalation method is said to be much more sensitive in this regard, no previous study has measured its sensitivity. Accordingly, in 15 patients (4 men, 11 women, aged 38 to 67 years) without intracardiac shunting, hydrogen inhalation was performed 1) without and 2) with an artificially created femoral arteriovenous shunt of known size, and cardiac output was measured by thermodilution. For the 15 subjects with cardiac outputs of 3.64 to 8.10 liters/min, shunts of 22 to 248 ml/min were created, so that the shunts ranged from 0.5% to 3.3%. Hydrogen inhalation detected all shunts greater than or equal to 1.3% (Qp/Qs greater than or equal to 1.01). Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods.     

Shunt quantification by mathematical analysis of indicator dilution curves.

Mathematical models are presented for describing and analyzing indicator dilution curves recorded in patients with intracardiac and great vessel shunts. The models treat individual segments of the circulation as linear system blocks, each having, at its output, a characteristic time response to a rapid injection of indicator at its input. These blocks are combined in feedback and feed-forward configurations to simulate left-to-right, right-to-left, and bidirectional shunts. A shunt analysis algorithm, using discrete analogs of the linear system models, was implemented in a computer program and used to analyze thermodilution curves recorded in patients with congenital heart defects. Results are presented comparing shunt fractions obtained from thermodilution curve analyses with oximetrically determined values in 20 patients. Comparing left-to-right shunts measured by the two methods, the mean systematic difference was 0.7% of pulmonary flow and the standard deviation was 7.6% of pulmonary flow. Statistical validation of the bidirectional shunt method will require acquisition and analysis of more data; however, reasonable shunt fractions were computed in five cases studied and good agreement with oximetric determinations was obtained in two cases where complete oximetric data were available.     

Shunt Quantification by Mathematical Analysis of Indicator Dilution Curves

Mathematical models are presented for describing and analyzing indicator dilution curves recorded in patients with intracardiac and great vessel shunts. The models treat individual segments of the circulation as linear system blocks, each having, at its output, a characteristic time response to a rapid injection of indicator at its input. These blocks are combined in feedback and feed-forward configurations to simulate left-to-right, right-to-left, and bidirectional shunts. A shunt analysis algorithm, using discrete analogs of the linear system models, was implemented in a computer program and used to analyze thermodilution curves recorded in patients with congenital heart defects. Results are presented comparing shunt fractions obtained from thermodilution curve analyses with oximetrically determined values in 20 patients. Comparing left-to-right shunts measured by the two methods, the mean systematic difference was 0.7% of pulmonary flow and the standard deviation was 7.6% of pulmonary flow. Statistical validation of the bidirectional shunt method will require acquisition and analysis of more data; however, reasonable shunt fractions were computed in five cases studied and good agreement with oximetric determinations was obtained in two cases where complete oximetric data were available.     

Pulse Densitometer Indocyanine Green Dilution Curves: A Simple Applicable and Accurate Method for Determination of Cardiac Shunts

Objective. Adequate hemodynamic evaluation is crucial in the management of patients with congenital heart disease. Although non‐invasive diagnostic tools have reduced the need for invasive procedures, cardiac catheterization is still mandatory for absolute quantification of pressures, flows and vascular resistances in selected patients. We therefore investigated the feasibility of a new technique, non‐invasive pulse densitometry (PD) in patients with intracardiac shunts and compared its results with the established standards: cuvette densitometry (CD) and oximetry (OX). Design. Measurement method comparison study. Outcome measure. In 12 patients with intracardiac shunt, dye dilution curves, using both pulse and cuvette densitometry, were recorded and oximetry was performed. Left‐to‐right shunt expressed as percentage of pulmonary blood flow Qp, was calculated from dye dilution and oximetry. In 4 patients with atrial septal defect, dye dilution curves were also recorded after closure of the defect with a device. Results. The mean difference ± SD between the shunt derived from PD and CD was 2.8 ± 10.0% of Qp, 95% confidence interval ?2.5 to 8.2. (Shunt‐PD vs. Shunt‐CD was 32.3 ± 23.9% vs. 29.5 ± 23.9% of Qp resp., n = 16). The mean difference ± SD between the shunt derived from PD and OX was 0.8 ± 9.8% of Qp, 95% confidence interval ?5.4 to 7.0 (Shunt‐PD vs. Shunt‐OX was 41.5 ± 20.3% vs. 40.7 ± 19.7% of Qp resp., n = 12). Conclusion. Transcutaneous recording of dye dilution curves with a pulse dye densitometer allows easy and accurate quantification of intracardiac left‐to‐right shunt flows over a wide range in both children and adults with congenital heart diseases.     

Quantification of left to right cardiac shunts by multiple deconvolution analysis

A new method for quantification of left to right cardiac shunts was studied in 17 patients scheduled for cardiac catheterization who had also undergone radionuclide angiocardiography. The observed pulmonary transit curve was deconvoluted in two different ways: (1) by the superior vena caval (“bolus”) time-activity curve, to yield the deconvoluted pulmonary transit curve, which represented the theoretical pulmonary transit curve with a perfect bolus injection, and (2) by the right ventricular time-activity curve, to yield the pulmonary transfer function, which represented the theoretical pulmonary transit curve with a perfect bolus injection and with no intracardiac shunts. The pulmonary transfer function was superimposed on the deconvoluted pulmonary transit curve, and the area A under it obtained. The pulmonary transfer function was then subtracted from the deconvoluted pulmonary transit curve. The pulmonary transfer function was scaled to fit the resulting shunt recirculation peak in the difference curve, and the area B under this scaled pulmonary transfer function obtained. Shunt size was quantified as the pulmonary (QP) to systemic (QS) flow ratio QP/QS = A/(A − B). The method correlated closely with oximetry (r = 0.93). Use of this multiple deconvolution analysis technique provides accurate shunt quantification and reduces subjective operator decisions.     

Calculation of intracardiac shunt using Doppler echocardiography

The purpose of this study was to assess the accuracy of a quantitative two-dimensional Doppler echocardiographic method for estimation of intracardiac shunts. The ratio of pulmonary to systemic flow (Qp/Qs) was evaluated by duplex Doppler echocardiography in 20 patients with various intracardiac shunts. Right and left ventricular stroke volumes (RSV, LSV) were determined from the recordings of ejection blood flow velocity and diameter at the level of the pulmonary and aortic orifices in each ventricular outflow tract. The ratio RSV/LSV, determined by duplex Doppler echocardiography, was compared with Qp/Qs by oxymetry. The Doppler echocardiograms were of sufficient quality for shunt calculation in 15/20 patients (75%). The RSV/LSV for ten normal subjects was 0.99 +/- 0.05 (mean +/- SD), whereas the RSV/LSV for 15 patients with intracardiac shunts, 2.6 +/- 0.5, was significantly higher than that for normal subjects (p less than 0.01). In 12/15 patients, the Doppler study estimated the severity of intracardiac shunting correctly. The presence of complex anatomic situations, a wide pulmonary artery or significant semilunar regurgitation seem to have a negative impact on the Doppler echocardiographic shunt calculation. Our findings indicate that, with a few limitations, the Doppler index RSV/LSV is clinically useful in the estimation of the magnitude of the shunt flow in patients with intracardiac shunts.     

Echocardiographic evaluation of the significance of shunt in secondary communications and in partial abnormal pulmonary venous returns]

Although echocardiography has been useful in diagnosing significant left-to-right shunts at the atrial level, few studies using this technique to quantitate shunt size have been performed. Echocardiograms and hemodynamic data from 28 patients, ages 15 to 58 (mean : 30 years) were reviewed. Twenty patients had isolated atrial septal defects (ASD), 6 patients has associated partial pulmonary venous returns (PPVR) and 2 patients had isolated PPVR. Echocardiograms in the supine position were performed within 24 hours preceding cardiac catheterization. The presence or absence of paradoxical septal motion was noted and right ventricular diameter index (RVDE : right ventricular diameter/body surface area) was calculated. Hemodynamic parameters studied included pulmonary to systemic flow ratio (Qp/Qs) determined by oxymetry, right ventricular pressure (RVP) and pulmonary resistance (PR). One patient with a Qp/Qs of 1.3 had normal septal motion. Type A paradoxical septal motion was noted in 22 cases, type B in 5 cases. For these 27 patients, the average RVDI was 2.42 (range 1.45 to 3.7), Qp/Qs ranged from 1.5 to 5 (mean : 2.45), RVP from 23 to 71 mmHg (mean : 39) and PR from 0.6 to 4 units (mean : 1.79). A very strons correlation between RVDI and Qp/Qs was observed from equation Qp/Qs : 1.19 RVDI-0.43 with a standard error of 0.4. This relationship was not altered by either RVP or PR values, which also had no apparent correlation with RVDI. This study indicates that echocardiographic measurement of RVDI is a reliable and non-invasive method of evaluating the size of left to right shunts at the atrial level.     

Quantification of left to right atrial shunts with velocity-encoded cine nuclear magnetic resonance imaging.

OBJECTIVES. The purpose of this study was to evaluate the ability of velocity-encoded nuclear magnetic resonance (NMR) imaging to quantify left to right intracardiac shunts in patients with an atrial septal defect. BACKGROUND. Quantification of intracardiac shunts is clinically important in planning therapy. METHODS. Velocity-encoded NMR imaging was used to quantify stroke flow in the aorta and in the main pulmonary artery in a group of patients who were known to have an increased pulmonary to systemic flow ratio (Qp/Qs). The velocity-encoded NMR flow data were used to calculate Qp/Qs, and these values were compared with measurements of Qp/Qs obtained with oximetric data derived from cardiac catheterization and from stroke volume measurements of the two ventricles by using volumetric data from biphasic spin echo and cine NMR images obtained at end-diastole and end-systole. RESULTS. Two independent observers measured Qp/Qs by using velocity-encoded NMR imaging in 11 patients and found Qp/Qs ranging from 1.4:1 to 3.9:1. These measurements correlated well with both oximetric data (r = 0.91, SEE = 0.35) and ventricular volumetric data (r = 0.94, SEE = 0.30). Interobserver reproducibility for Qp/Qs by velocity-encoded NMR imaging was good (r = 0.97, SEE = 0.20). CONCLUSIONS. Velocity-encoded NMR imaging is an accurate and reproducible method for measuring Qp/Qs in left to right shunts. Because it is completely noninvasive, it can be used to monitor shunt volume over time.     

Assessment of the intracardiac left to right shunts with a single scintillation probe

In order to assess the accuracy of pulmonary time-activity curves obtained at bedside with a single scintillation probe and Technetium-99m-labelled erythrocytes, pulmonary to systemic flow ratio (Qp:Qs) was calculated for radionuclide and hemodynamic investigations in 104 patients with suspected intracardiac left to right shunts. Cardiac catheterization confirmed the presence of shunts in 76 patients. Pulmonary time-activity curve was 100% sensitive, 88% specific, and 96% accurate in detecting the shunt. Correlation between the radionuclide and hemodynamic Qp:Qs was excellent (r = 0.93). Results were classified in four quantitative categories according to the Qp:Qs values. In 76 patients (73%) radionuclide and hemodynamic data fell in the same category. We conclude that radionuclide pulmonary time-activity curves generated with a scintillation probe is a reliable method in quantitative assessment of intracardiac left to right shunts.     

Determination of left to right shunt by thermodilution in patients with ventricular septal defect

A modified thermodilution technique was used to determine the quantity of shunt in patients suffering from congenital heart disease with a left to right shunt. In our modification, the thermistor was placed within the pulmonary artery and an indicator was injected into both sides of the heart. In a series of 33 cardiac catheterizations in children (1-17 years) with ventricular septal defect (VSD), pulmonary blood flow (Qp), systemic blood flow (Qs) and the ratio of Qp to Qs (Qp/Qs) were determined by this and ordinary oximetry (Fick) methods. Correlation coefficients between indexes obtained by these methods were 0.54 (Qp), 0.78 (Qs), and 0.75 (Qp/Qs). The estimates of Qp and Qp/Qs obtained by thermodilution were smaller than those obtained by the Fick method. This modification of thermodilution is simple, rapid, and useful in clinical practice.     

Accuracy of electrical impedance cardiography for measuring cardiac output in children with congenital heart defects

This study determined whether noninvasive electrical impedance cardiography accurately measures systemic blood flow (cardiac output) in children with congenital heart defects. A total of 37 patients ranging in age from 2 to 171 months underwent complete right- and left-sided heart catheterizations that included simultaneous Fick and impedance measurement of cardiac output. Based on the diagnosis, 4 groups were formed consisting of a control group (n = 11) with no shunts, a group with intracardiac left-to-right shunting and an atrial septal defect (n = 7), another with a ventricular septal defect (n = 12) and an extracardiac left-to-right shunting with patent ductus arteriosus group (n = 7). Impedance values for systemic blood flow were compared with systemic and pulmonary blood flow obtained by the direct Fick method with measured oxygen consumption. The difference between impedance and Fick systemic blood flow was less than or equal to 5% in each of the 4 groups. The highest correlation between impedance and Fick systemic blood flow was with the atrial septal defect group (r = 0.89) and lowest with the ventricular septal defect and control (r = 0.69) groups. Fick pulmonary blood flow was significantly greater than impedance or Fick systemic flow in all 3 shunt groups. Impedance cardiography accurately measured systemic blood flow in children without shunts or valvular insufficiency. Likewise, systemic blood flow was accurately measured by impedance in the presence of intracardiac left-to-right shunts (atrial and ventricular septal defects) and extracardiac left-to-right shunts (patent ductus arteriosus).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative radionuclide angiocardiography: Detection and quantitation of left to right shunts

In 105 patients detection and quantitation of left to right shunts was performed using quantitative radionuclide angiocardiography. The radionuclide angiocardiograms were acquired and analyzed by a gamma camera interfaced to a digital computer system. Pulmonary to systemic flow ($\text{Qp}\text{Qs}$) ratios were calculated by analysis of pulmonary time-activity histograms using a gamma variate model. All patients were studied with cardiac catheterization, left ventricular angiocardiography and radionuclide angiocardiography. The radionuclide method allowed precise detection and quantitation of left to right shunts with a $\text{Qp}\text{Qs}$ ratio of 1.2 to 3.0. There was good agreement between the $\text{Qp}\text{Qs}$ ratio calculated by oximetry at cardiac catheterization and radionuclide angiocardiography (r = 0.94). The information gathered with this nontraumatic method appears sufficiently reliable to be used in the management of patients.     

Value and limitations of sequential technetium 99m angiocardiography in the detection, localization and quantification of left-right intracardiac shunts apropos of 110 cases]

A comparative study of the diagnosis of intracardiac left-to-right shunts by isotope radiography on the one hand and oxymetry, abnormal catheter trajectory and angiocardiography on the other, was performed on a series of 110 patients, comprising 12 normals, 46 valvulopathies or cardiomyopathies without shunts, 23 ASDs, 22 VSDs, and 7 other shunts. Intravenous injection of Technetium 99 m with scintigraphic imagery and interpretation of time-activity curves detected even small left-to-right shunts and appeared to be more sensitive than oxumetry. The estimation of the size of the shunt correlated well with oxymetry for VSDs but not for ASDs. The localisation of the shunt was more difficult. The atrial level of the defect was detected in some but not the majority of cases. The isotopic technique appeared unreliable in the presence of severe haemodynamic disturbances. The isotopic method is a quick means of detecting left-to-right shunts without measurable risk, particularly useful in the investigation of children and young adults thought to have left-to-right shunts.     

Radionuclide ventriculography: A noninvasive method for the detection and quantification of left-to-right shunts in atrial septal defect

The present investigation was undertaken to assess a new scintigraphic method for the diagnosis of left-to-right shunts due to atrial septal defect based on the differing stroke volumes of left and right ventricles and to compare it with oxymetric data. Radionuclide ventriculography was carried out after injection of 20 mCi ^99mtechnetium-labeled red blood cells. Time-activity curves were obtained from the left and right ventricular regions, and the ratio (A) of end-diastolic-end-systolic count rate differences for the left and right ventricles was calculated. The left-to-right shunt (in percent of the-pulmonary flow rate) is then given as 100 × (1 – A/1.43); 1.43 being the previously determined mean value of A in 66 normal patients. In 16 patients with an atrial septal defect and/or partial anomalous pulmonary venous connection a correlation of r = 0.81 was found between those shunts determined by the scintigraphic method and those calculated by oxymetric data. The specificity of the method and the sensitivity in detecting left-to-right shunts exceeding 30% are high. The method is practical and already widely used for determination of ejection fraction, end-diastolic volume and other factors. The combination of this technique with other methods for shunt diagnosis such as gamma-fit analysis may prove of special value.     

Direct measurement of cardiac output by gated equilibrium blood pool scintigraphy: Validation of scintigraphic volume measurements by a nongeometric technique

A nongeometric technique for the determination of left ventricular volumes from the count data derived from gated equilibrium blood pool scans was previously described and validated by the demonstration of an excellent correlation between the derived data and angiographically determined left ventricular volumes. To provide a further prospective evaluation of this method and to validate its ability to determine stroke volume and cardiac output by a technique that is itself independent of geometric assumptions, simultaneous measurements of cardiac output by the thermodilution technique and gated scintigraphy were performed in 21 patients without valve regurgitation or intracardiac shunts. To substantiate the reliability of scintigraphic measurements at high levels of cardiac output, seven patients had multiple measurements of cardiac output at rest and during an infusion of isoproterenol. There was an excellent correlation between thermodilution and scintigraphic values for cardiac output (scan cardiac output = 0.99 thermodilution cardiac output ? 0.005 liters/min; n = 31, standard error of the estimate [SEE]= 0.175 liters/min, r = 0.97) as well as between thermodilution and scintigraphic stroke volumes (scan stroke volume = 1.03 thermodilution stroke volume ? 2.8 ml; n = 31, SEE = 2.5 ml, r = 0.95). In addition, the relation between scintigraphic and angiographic measurements of left ventricular volumes continued to be excellent: In 15 patients with technically adequate angiograms, scintigraphic left ventricular volume = 0.90 angiographic left ventricular volume + 7 ml (n = 30, SEE = 10 ml, r = 0.91). Thus, this study further validates the nongeometric method of measuring left ventricular volumes with gated scintigraphy and demonstrates its ability to measure left ventricular stroke volume and cardiac output reliably.     

Lung mechanics in infants with left-to-right shunt congenital heart disease

To clarify which hemodynamic measurement correlates best with lung mechanics in infants with congenital heart disease and left-to-right shunts, dynamic pulmonary function tests and echocardiography were performed in 26 infants with such disease (study infants) and in 37 normal, healthy infants (control infants). The tidal volume and pulmonary compliance (C_L) were lower and airway resistance higher in infants with congenital heart disease than in control infants. A significant correlation was demonstrated between C_L, expiratory resistance (R_e), and the right pulmonary artery-to-aortic size ratio (RPA/DAO). C_L and R_e also correlated well with the corrected acceleration time √RR ratio (ACT/√RR: ACT, acceleration time and RR: length of the cardiac cycle) of pulmonary flow velocity. Stepwise multiple regression analysis revealed that RPA/DAO correlated best with both C_L and R_e. It is concluded that infants with congenital heart disease and left-to-right shunts have lower lung compliance and higher expiratory airway resistance than normal children, and that RPA/DAO is the echocardiographic parameter that correlates best with the changes in lung mechanics. Pediatr Pulmonol. 1996; 21:42–47. © 1996 Wiley-Liss, Inc.     

Measurement of systemic and pulmonary blood flow and QP/QS ratio using Doppler and two-dimensional echocardiography

A noninvasive method for measuring systemic and pulmonary blood flow using Doppler velocimetry combined with 2-dimensional (2-D) echocardiography has been developed. High correlations were found between Fick- and Doppler-derived indexed measurements of systemic and pulmonary flow as well as the pulmonary to systemic flow ratio in 33 patients undergoing cardiac catheterization (systemic flow [n = 28], r = 0.78; pulmonary flow [n = 21], r = 0.88; Qp/Qs ratio [n = 24], r = 0.85). The random errors of the 2 methods were not significantly different. Outflow tract obstruction, semilunar valve regurgitation, and patent ductus arteriosus were the only lesions in which limitations to the use of this method were encountered. We anticipate that this method will be of use in initial and serial evaluations of adult and pediatric patients with low cardiac output or intracardiac shunts.     

Computer analysis of oximetry data in cardiac catheterization

An on-line computer technique is described for the detection and quantitation of left-to-right shunts. The computer used Student's t test to evaluate the probability that variations in right heart oxygen saturations were due to left-to-right shunts. The computer method was found to compare favorably to the present step-up method of detecting left-to-right shunts. The computer also calculated pulmonary blood flow, systemic blood flow, their ratio, and shunt blood flow as accurately as standard methods, as evidenced by correlation coefficients of 0.98, 0.94, 0.95, and 0.71 between the computer and hand calculations.     

Usefulness of anatomic parameters derived from two-dimensional echocardiography for estimating magnitude of left to right shunt in patients with atrial septal defect

The ability of two-dimensional echocardiography (2DE) to quantitate the atrial septal defect size and left-to-right shunt magnitude was examined in 75 adult patients with simple ostium secundum atrial septal defect (ASD) with left-to-right shunts of 19-92% of systemic flow as determined by oximetry. The ASD was visualized in 71 of 75 (95%) patients utilizing subcostal 2DE, and the end-systolic atrial septal defect diameters in subcostal 2DE (ASDe) were measured. The maximal diameters of ASD measured during operation (ASDop) were obtained in 45 of these patients, who then underwent surgical ASD repair. The correlation between ASDe and ASDop was high (r = 0.91, p less than 0.001), indicating accuracy of quantitating defect size via subcostal 2DE approach. However, the correlation between the left-to-right shunt magnitude and ASDe was only fair (r = 0.76, p less than 0.01). In large ASDe the shunts varied greatly, while in small ASDe the shunts increased proportionally with increasing sizes of ASD. In addition, the ratio of left-to-right ventricular diameter (RVD/LVD) was determined. The RVD/LVD correlated relatively well with the shunt magnitudes (r = 0.83, p less than 0.001). Using the two new echocardiographic parameters of ASDe and RVD/LVD, a high percentage (85%) of patients with a large left-to-right shunt requiring surgical closure can be identified. All 43 patients with ASDe greater than 2.0 cm and RVD/LVD greater than 1.1 had a left-to-right shunt greater than 40%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radionuclide Quantitation of Left-to-Right Cardiac Shunts in Children

Summary: Radionuclide quantitation of left-to-right cardiac shunts in children. B. M. Mcllveen, R. Höschl, I. P. C. Murray, R. M. McCredie, P. Chidiac, D. Marriott and J. Beveridge, Aust N.Z. J. Med., 1978, 8, pp. 500–508.
In order to evaluate the clinical usefulness of radionuclide methods measuring the magnitude of left-to-right cardiac shunts, a comparison has been made of the results obtained using these procedures with those estimated by cardiac catheterization. Seventy children in whom the presence or absence of a shunt had been established, were studied. Two methods for radionuclide shunt quantitation, the pulmonary to systemic blood flow ratio (Qp/Qs) of Maltz and Treves and their modified C2/C1, were evaluated. The former was found to be superior and showed a high correlation of shunt size with the catheter results. With attention to the performance of the investigation and in the data analysis, good discrimination can be achieved between normal patients and those with shunts. Because of the atraumatic nature of the investigation, it is concluded that the procedure is of value in the diagnosis of a cardiac murmur, the assessment of postoperative patients and the follow-up of patients known to have a small shunt.