Niti M. Dhutia

Test–retest repeatability of cardiopulmonary exercise test variables in patients with cardiac or respiratory disease

Background The test–retest reliability for multiple cardiopulmonary exercise test (CPX) variables has not been compared in a single study and the influence of different diseases on test–retest reliability has not been examined. We investigated different measures of test–retest reliability for multiple variables and compared them by category of cardiac or respiratory disease. Methods Patients with chronic obstructive airways disease (n = 24), heart failure (n = 43), or severe mitral valve disease (n = 26) were recruited into a prospective study. Each patient underwent two bicycle ergometer tests; the first, a familiarization test, with a 10 W/min ramp, and the second a personalized ramp based on the results of the familiarization test to elicit maximal effort within 8–10 min. Intraclass correlation coefficients (ICC) and coefficients of variation between the two tests were calculated. Influence of potential modifiers was assessed using repeated measures analysis of variance. Results Peak VO2 (ICC 0.95, 95% CI 0.94–0.97), oxygen uptake efficiency slope (ICC 0.93, 95% CI 0.90–0.95), O2 pulse (ICC 0.96, 95% CI 0.94–0.97), and the VE/VCO2 ratio at the nadir (ICC 0.92, 95% CI 0.89–0.95) all showed excellent test–retest reliability, with within-subject coefficients of variation <0.12. VO2 at the anaerobic threshold (ICC 0.84, 95% CI 0.78–0.89) and the VE/VCO2 slope (ICC 0.88, 95% CI 0.79–0.93) showed good test–retest reliability, although inferior to peak VO2. Age, gender, body mass index, disease aetiology, protocol change, and intertest interval did not affect the reliability of most variables. Conclusions CPX showed high test–retest reliability; certain variables such as peak VO2 and oxygen uptake efficiency slope outperform others. These results identify which variables are most suitable for serial testing of patients with three common disease aetiologies owing to their superior reproducibility.

Aortic Reservoir Pressure Corresponds to Cyclic Changes in Aortic Volume: Physiological Validation in Humans

Objective—Aortic reservoir pressure indices independently predict cardiovascular events and mortality. Despite this, there has never been a study in humans to determine whether the theoretical principles of the mathematically derived aortic reservoir pressure (RPderived) and excess pressure (XPderived) model have a real physiological basis. This study aimed to directly measure the aortic reservoir (ARdirect; by cyclic change in aortic volume) and determine its relationship with RPderived, XPderived, and aortic blood pressure (BP). Approach and Results—Ascending aortic BP and Doppler flow velocity were recorded via intra-arterial wire in 10 men (aged 62±12 years) during coronary artery bypass surgery. Simultaneous ascending aortic transesophageal echocardiography was used to measure ARdirect. Published mathematical formulae were used to determine RPderived and XPderived. ARdirect was strongly and linearly related to RPderived during systole (r=0.988; P<0.001) and diastole (r=0.985; P<0.001). Peak cross-correlation (r=0.98) occurred at a phase lag of 0.004 s into the cardiac cycle, suggesting close temporal agreement between waveforms. The relationship between aortic BP and ARdirect was qualitatively similar to the cyclic relationship between aortic BP and RPderived, with peak cross-correlations occurring at identical phase lags (ARdirect versus aortic BP, r=0.96 at 0.06 s; RPderived versus aortic BP, r=0.98 at 0.06 s). Conclusions—RPderived is highly correlated with changes in proximal aortic volume, consistent with its physiological interpretation as corresponding to the instantaneous volume of blood stored in the aorta. Thus, aortic reservoir pressure should be considered in the interpretation of the central BP waveform.

Aortic Reservoir Pressure Corresponds to Cyclic Changes in Aortic Volume

Objective—Aortic reservoir pressure indices independently predict cardiovascular events and mortality. Despite this, there has never been a study in humans to determine whether the theoretical principles of the mathematically derived aortic reservoir pressure (RPderived) and excess pressure (XPderived) model have a real physiological basis. This study aimed to directly measure the aortic reservoir (ARdirect; by cyclic change in aortic volume) and determine its relationship with RPderived, XPderived, and aortic blood pressure (BP). Approach and Results—Ascending aortic BP and Doppler flow velocity were recorded via intra-arterial wire in 10 men (aged 62±12 years) during coronary artery bypass surgery. Simultaneous ascending aortic transesophageal echocardiography was used to measure ARdirect. Published mathematical formulae were used to determine RPderived and XPderived. ARdirect was strongly and linearly related to RPderived during systole (r=0.988; P<0.001) and diastole (r=0.985; P<0.001). Peak cross-correlation (r=0.98) occurred at a phase lag of 0.004 s into the cardiac cycle, suggesting close temporal agreement between waveforms. The relationship between aortic BP and ARdirect was qualitatively similar to the cyclic relationship between aortic BP and RPderived, with peak cross-correlations occurring at identical phase lags (ARdirect versus aortic BP, r=0.96 at 0.06 s; RPderived versus aortic BP, r=0.98 at 0.06 s). Conclusions—RPderived is highly correlated with changes in proximal aortic volume, consistent with its physiological interpretation as corresponding to the instantaneous volume of blood stored in the aorta. Thus, aortic reservoir pressure should be considered in the interpretation of the central BP waveform.

A novel fully automated method for mitral regurgitant orifice area quantification

Background Effective regurgitant orifice area (EROA) in mitral regurgitation (MR) is difficult to quantify. Clinically it is measured using the proximal isovelocity surface area (PISA) method, which is intrinsically not automatable, because it requires the operator to manually identify the mitral valve orifice. We introduce a new fully automated algorithm, (“AQURO”), which calculates EROA directly from echocardiographic colour M-mode data, without requiring operator input. Methods Multiple PISA measurements were compared to multiple AQURO measurements in twenty patients with MR. For PISA analysis, three mutually blinded observers measured EROA from the four stored video loops. For AQURO analysis, the software automatically processed the colour M-mode datasets and analysed the velocity field in the flow-convergence zone to extract EROA directly without any requirement for manual radius measurement. Results Reproducibility, measured by intraclass correlation (ICC), for PISA was 0.80, 0.83 and 0.83 (for 3 observers respectively). Reproducibility for AQURO was 0.97. Agreement between replicate measurements calculated using Bland-Altman standard deviation of difference (SDD) was 21,17 and 17mm2for the three respective observers viewing independent video loops using PISA. Agreement between replicate measurements for AQURO was 6, 5 and 7mm2for automated analysis of the three pairs of datasets. Conclusions By eliminating the need to identify the orifice location, AQURO avoids an important source of measurement variability. Compared with PISA, it also reduces the analysis time allowing analysis and averaging of data from significantly more beats, improving the consistency of EROA quantification. AQURO, being fully automated, is a simple, effective enhancement for EROA quantification using standard echocardiographic equipment.

A new automated system to identify a consistent sampling position to make tissue Doppler and transmitral Doppler measurements of E, E′ and E/E′

Background Transmitral pulse wave (PW) Doppler and annular tissue Doppler velocity measurements provide valuable diagnostic and prognostic information. However, they depend on an echocardiographer manually selecting positions to make the measurements. This is time-consuming and open to variability, especially by less experienced operators. We present a new, automated method to select consistent Doppler velocity sites to measure blood flow and muscle function. Methods Our automated algorithm combines speckle tracking and colour flow mapping to locate the septal and lateral mitral valve annuli (to measure peak early diastolic velocity, E′) and the mitral valve inflow (to measure peak inflow velocity, E). We also automate peak velocity measurements from resulting PW Doppler traces. The algorithm-selected locations and time taken to identify them were compared against a panel of echo specialists — the current “gold standard”. Results The algorithm identified positions to measure Doppler velocities within 3.6 ± 2.2 mm (mitral inflow), 3.2 ± 1.8 mm (septal annulus) and 3.8 ± 1.5 mm (lateral annulus) of the consensus of 3 specialists. This was less than the average 4 mm fidelity with which the specialists could themselves identify the points. The automated algorithm could potentially reduce the time taken to make these measurements by 60 ± 15%. Conclusions Our automated algorithm identified sampling positions for measurement of mitral flow, septal and lateral tissue velocities as reliably as specialists. It provides a rapid, easy method for new specialists and potentially non-specialists to make automated measurements of key cardiac physiological indices. This could help support decision-making, without introducing delay and extend availability of echocardiography to more patients.

Automated Aortic Doppler Flow Tracing for Reproducible Research and Clinical Measurements

In clinical practice, echocardiographers are often unkeen to make the significant time investment to make additional multiple measurements of Doppler velocity. Main hurdle to obtaining multiple measurements is the time required to manually trace a series of Doppler traces. To make it easier to analyze more beats, we present the description of an application system for automated aortic Doppler envelope quantification, compatible with a range of hardware platforms. It analyses long Doppler strips, spanning many heartbeats, and does not require electrocardiogram to separate individual beats. We tested its measurement of velocity-time-integral and peak-velocity against the reference standard defined as the average of three experts who each made three separate measurements. The automated measurements of velocity-time-integral showed strong correspondence (R2 = 0.94) and good Bland-Altman agreement (SD = 1.39 cm) with the reference consensus expert values, and indeed performed as well as the individual experts ( R2 = 0.90 to 0.96, SD = 1.05 to 1.53 cm). The same performance was observed for peak-velocities; ( R2 = 0.98, SD = 3.07 cm/s) and ( R2 = 0.93 to 0.98, SD = 2.96 to 5.18 cm/s). This automated technology allows > 10 times as many beats to be analyzed compared to the conventional manual approach. This would make clinical and research protocols more precise for the same operator effort.

Frame rate required for speckle tracking echocardiography: A quantitative clinical study with open-source, vendor-independent software

OBJECTIVES To determine the optimal frame rate at which reliable heart walls velocities can be assessed by speckle tracking. BACKGROUND Assessing left ventricular function with speckle tracking is useful in patient diagnosis but requires a temporal resolution that can follow myocardial motion. In this study we investigated the effect of different frame rates on the accuracy of speckle tracking results, highlighting the temporal resolution where reliable results can be obtained. MATERIAL AND METHODS 27 patients were scanned at two different frame rates at their resting heart rate. From all acquired loops, lower temporal resolution image sequences were generated by dropping frames, decreasing the frame rate by up to 10-fold. RESULTS Tissue velocities were estimated by automated speckle tracking. Above 40 frames/s the peak velocity was reliably measured. When frame rate was lower, the inter-frame interval containing the instant of highest velocity also contained lower velocities, and therefore the average velocity in that interval was an underestimate of the clinically desired instantaneous maximum velocity. CONCLUSIONS The higher the frame rate, the more accurately maximum velocities are identified by speckle tracking, until the frame rate drops below 40 frames/s, beyond which there is little increase in peak velocity. We provide in an online supplement the vendor-independent software we used for automatic speckle-tracked velocity assessment to help others working in this field.

Automated speckle tracking algorithm to aid on-axis imaging in echocardiography

Abstract. Obtaining a “correct” view in echocardiography is a subjective process in which an operator attempts to obtain images conforming to consensus standard views. Real-time objective quantification of image alignment may assist less experienced operators, but no reliable index yet exists. We present a fully automated algorithm for detecting incorrect medial/lateral translation of an ultrasound probe by image analysis. The ability of the algorithm to distinguish optimal from sub-optimal four-chamber images was compared to that of specialists—the current “gold-standard.” The orientation assessments produced by the automated algorithm correlated well with consensus visual assessments of the specialists (r=0.87) and compared favourably with the correlation between individual specialists and the consensus, 0.82±0.09. Each individual specialist’s assessments were within the consensus of other specialists, 75±14% of the time, and the algorithm’s assessments were within the consensus of specialists 85% of the time. The mean discrepancy in probe translation values between individual specialists and their consensus was 0.97±0.87  cm, and between the automated algorithm and specialists’ consensus was 0.92±0.70  cm. This technology could be incorporated into hardware to provide real-time guidance for image optimisation—a potentially valuable tool both for training and quality control.

Doppler assessment of aortic stenosis: a 25-operator study demonstrating why reading the peak velocity is superior to velocity time integral

Abstract Aims Measurements with superior reproducibility are useful clinically and research purposes. Previous reproducibility studies of Doppler assessment of aortic stenosis (AS) have compared only a pair of observers and have not explored the mechanism by which disagreement between operators occurs. Using custom-designed software which stored operators’ traces, we investigated the reproducibility of peak and velocity time integral (VTI) measurements across a much larger group of operators and explored the mechanisms by which disagreement arose. Methods and results Twenty-five observers reviewed continuous wave (CW) aortic valve (AV) and pulsed wave (PW) left ventricular outflow tract (LVOT) Doppler traces from 20 sequential cases of AS in random order. Each operator unknowingly measured each peak velocity and VTI twice. VTI tracings were stored for comparison. Measuring the peak is much more reproducible than VTI for both PW (coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coefficient of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early and late parts of the envelope are difficult to trace reproducibly. Dimensionless index improves reproducibility because operators tended to consistently over-read or under-read on LVOT and AV traces from the same patient (coefficient of variation 9.3 vs. 17.1%; P < 0.001). Conclusion It is far more reproducible to measure the peak of a Doppler trace than the VTI, a strategy that reduces measurement variance by approximately six-fold. Peak measurements are superior to VTI because tracing the steep slopes in the early and late part of the VTI envelope is difficult to achieve reproducibly.

Impact of Chronic Hypoxia on Proximal Pulmonary Artery Wave Propagation and Mechanical Properties in Rats

Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals/group), animals underwent transthoracic echocardiography and PA catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis was performed. Artery rings obtained from the pulmonary trunk, right and left PAs, and aorta were subjected to a tensile test to rupture. Collagen and elastin content were determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus, and wall viscosity increased, whereas the elastin-to-collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased, and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in hypoxic and normoxic animals with negligible wave reflection. In contrast, the aortic maximal elastic modulus remained unchanged, whereas wall viscosity decreased. In conclusion, there was no evidence of altered arterial wave propagation in proximal PAs of hypoxic rats while the extracellular matrix protein composition was altered and collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo. NEW & NOTEWORTHY In rats exposed to chronic hypoxia, we have shown that pulse wave velocity in the proximal pulmonary arteries increased and pressure dependence of the pulse wave velocity was steeper in vivo than ex vivo leading to a more prominent increase in vivo.