Left ventricular rotational mechanics in Tanzanian children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a common inherited hemoglobinopathy. Adults with SCD manifest both systolic and diastolic cardiac dysfunction, though the age of onset of dysfunction has not been defined. Left ventricular (LV) rotational mechanics have not been studied in children with SCD. The aim of this study was to investigate whether cardiac rotational mechanics differed between children with SCD and age-matched controls. METHODS: Basal and apical LV short-axis images were acquired prospectively in 213 patients with SCD (mean age, 14.1 ± 2.6 years) and 49 controls (mean age, 13.3 ± 2.8 years) from the Muhimbili Sickle Cohort in Dar es Salaam, Tanzania. The magnitude of basal and apical rotation, net twist angle, torsion, and untwist rate were obtained by two-dimensional speckle-tracking. The timing of events was normalized to aortic valve closure. RESULTS: Mean basal rotation was significantly lower in patients with SCD compared with controls (P = .012), although no difference was observed in apical rotation (P = .37). No statistically significant differences in torsion or net twist angle were detected. Rotation rate at the apex (P = .001) and base (P = .0004) were significantly slower in subjects with SCD compared with controls. Mean peak untwisting rate was also significantly slower in patients with SCD (P = .006). No associations were found between hemoglobin concentration and apical rotation, basal rotation, net twist, and torsion. CONCLUSION: This study demonstrates alterations in LV rotational mechanics in children with SCD, including lower basal rotation, peak differential twist, and untwist rate. These abnormalities denote subclinical changes in LV systolic and diastolic performance in children with SCD. Future work may reveal an association between rotational metrics and long-term patient outcomes.

Measurement uncertainty in pulmonary vascular input impedance and characteristic impedance estimated from pulsed-wave Doppler ultrasound and pressure: clinical studies on 57 pediatric patients.

Pulmonary vascular input impedance better characterizes right ventricular (RV) afterload and disease outcomes in pulmonary hypertension compared to the standard clinical diagnostic, pulmonary vascular resistance (PVR). Early efforts to measure impedance were not routine, involving open-chest measurement. Recently, the use of pulsed-wave (PW) Doppler-measured velocity to non-invasively estimate instantaneous flow has made impedance measurement more practical. One critical concern remains with clinical use: the measurement uncertainty, especially since previous studies only incorporated random error. This study utilized data from a large pediatric patient population to comprehensively examine the systematic and random error contributions to the total impedance uncertainty and determined the least error prone methodology to compute impedance from among four different methods. We found that the systematic error contributes greatly to the total uncertainty and that one of the four methods had significantly smaller propagated uncertainty; however, even when this best method is used, the uncertainty can be large for input impedance at high harmonics and for the characteristic impedance modulus. Finally, we found that uncertainty in impedance between normotensive and hypertensive patient groups displays no significant difference. It is concluded that clinical impedance measurement would be most improved by advancements in instrumentation, and the best computation method is proposed for future clinical use of the input impedance.

Noninvasive methods for determining pulmonary vascular function in children with pulmonary arterial hypertension: application of a mechanical oscillator model.

OBJECTIVE: Noninvasive diagnostics for pulmonary arterial hypertension (PAH) have traditionally sought to predict main pulmonary artery pressure from qualitative or direct quantitative measures of the flow velocity pattern obtained from spectral Doppler ultrasound examination of the main pulmonary artery. A more detailed quantification of flow velocity patterns in the systemic circuit has been obtained by parameterizing the flow trace with a simple dynamic system model. Here, we investigate such a model's utility as a noninvasive predictor of total right heart afterload and right heart function. DESIGN: Flow velocity and pressure was measured within the main pulmonary artery during right heart catheterization of patients with normal hemodynamics (19 subjects, 20 conditions) and those with PAH undergoing reactivity evaluation (34 patients, 69 conditions). Our model parameters were obtained by least-squares fitting the model velocity to the measured flow velocity. RESULTS: Five parameter means displayed significant (P < .05) differences between normotensive and hypertensive groups. The model stiffness parameter correlated to actual pulmonary vascular resistance (r = 0.4924), pulmonary vascular stiffness (r = 0.6811), pulmonary flow (r = 0.6963), and stroke work (r = 0.7017), while the model initial displacement parameter had good correlation to stiffness (r = 0.6943) and flow (r = 0.6958). CONCLUSIONS: As predictors of total right heart afterload (resistance and stiffness) and right ventricle work, the model parameters of stiffness and initial displacement offer more comprehensive measures of the disease state than previous noninvasive methods and may be useful in routine diagnostic monitoring of patients with PAH.

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

BACKGROUND: Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. METHODS: Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. RESULTS: Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). CONCLUSIONS: Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

Extraction of pulmonary vascular compliance, pulmonary vascular resistance, and right ventricular work from single-pressure and Doppler flow measurements in children with pulmonary hypertension: a new method for evaluating reactivity: in vitro and clinical studies.

BACKGROUND: Current evaluation of pulmonary hypertension (PH) in children involves measurement of pulmonary vascular resistance (PVR); however, PVR neglects important pulsatile components. Pulmonary artery (PA) input impedance and ventricular power (VP) include mean and pulsatile effects and have shown promise as alternative measures of vascular function. Here we report the utility of pulsed-wave (PW) Doppler-measured instantaneous flow and pressure measurements for estimation of input impedance and VP and use this method to develop a novel parameter: reactivity in compliance. METHODS AND RESULTS: An in vitro model of the general pulmonary vasculature was used to obtain impedance and VP, measured by PW Doppler and a reference flow meter. The method was then tested in a preliminary clinical study in subjects with normal PA hemodynamics (n=4) and patients with PH undergoing reactivity evaluation (8 patients; 23 data points). In vitro results showed good agreement between the impedance spectra computed from both flow-measurement methods. Excellent correlation was seen in vitro between actual resistance and the zero-frequency (Z(o)) impedance value (r2=0.984). Excellent agreement was also found between Z(o) and PVR in the clinical measurements (y=1.075x+0.73; r=0.993). Furthermore, total VP and VP/cardiac output increased significantly with hypertension (128.73 to 365.91 mW and 2.42 to 6.69 mW x mL(-1) x s(-1), respectively). The first-harmonic value of impedance (Z1) was used as a measure of compliance reactivity; older patients exhibited markedly less compliance reactivity than did younger patients. CONCLUSIONS: Input impedance and VP calculated from Doppler measurements and a single-catheter pressure measurement provide comprehensive characterization of PH and reactivity.