Quantification of biventricular strain and assessment of ventriculo-ventricular interaction in pulmonary arterial hypertension using exercise cardiac magnetic resonance imaging and myocardial feature tracking.

BACKGROUND: Right ventricular (RV) failure is the main cause of mortality in pulmonary arterial hypertension (PAH). Exercise testing helps identify early RV maladaptation and systolic dysfunction and facilitates therapy. Myocardial strain has been shown to be more sensitive than ejection fraction (EF) in detecting subclinical ventricular contractile dysfunction. Chronic pressure overload in PAH had been associated with changes in left ventricular (LV) filling. PURPOSE: To compare biventricular strains and ventriculo-ventricular interaction in PAH and controls using cardiac magnetic resonance feature tracking (cMRI-FT) and to determine the reproducibility of strain analysis. STUDY TYPE: Prospective. POPULATION: Nine PAH and nine control subjects. FIELD STRENGTH/SEQUENCE: 1.5T MRI balanced steady state free precession. ASSESSMENT: RV and LV longitudinal strain (EllRV and EllLV ) were derived using the mid-axial images. Radial (ErrLV ) and circumferential strain (EccLV ) were derived using the mid-ventricular short-axis images. Relationships between strain and volumetric parameters were assessed at rest and during submaximal in-magnet exercise. STATISTICAL TESTS: Comparison of rest-to-exercise data between PAH and controls was analyzed using two-way repeated measures analysis of variance. The relationship between volumetric parameters and cMRI-FT were assessed using Pearson's correlation. Reproducibility was assessed by using Bland-Altman plots. RESULTS: PAH had significantly lower EllRV at rest (-16.6 ± 2.7 vs. -20.1 ± 3.6, P = 0.03) despite normal RVEF. During exercise, RV systolic contractile reserve measured by EllRV was significantly reduced in PAH (PInteraction = 0.02). In PAH, indexed RV end-systolic volume (ESVi) significantly correlated with EccLV and ErrLV at rest (r = -0.65 and r = -0.70, P < 0.05) and with ErrLV during exercise (r = -0.43, P < 0.05). High observer agreement was demonstrated. DATA CONCLUSION: Despite normal resting RVEF, RV systolic function and contractile reserve as measured by EllRV was significantly reduced in PAH. The close relation between RVESVi with EccLV and ErrLV provides evidence of systolic ventriculo-ventricular interaction in PAH. Exercise cMRI-FT may provide a quantitative metric for detection of subclinical RV dysfunction in PAH. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1427-1436.

Higher resolution cine imaging with compressed sensing for accelerated clinical left ventricular evaluation.

PURPOSE: To assess the clinical feasibility of a compressed sensing cine magnetic resonance imaging (MRI) sequence of both high temporal and spatial resolution (CS_bSSFP) in comparison to a balanced steady-state free precession cine (bSSFP) sequence for reliable quantification of left ventricular (LV) volumes and mass. MATERIALS AND METHODS: Segmented MRI cine images were acquired on a 1.5T scanner in 50 patients in the LV short-axis stack orientation using a retrospectively gated conventional bSSFP sequence (generalized autocalibrating partially parallel acquisition [GRAPPA] acceleration factor 2), followed by a prospectively triggered CS_bSSFP sequence with net acceleration factor of 8. Image quality was assessed by published criteria. Comparison of sequences was made in LV volumes and mass, image quality score, quantitative regional myocardial wall motion, and imaging time using Pearson's correlation, Bland-Altman and paired 2-tailed Student's t-test. RESULTS: Differences (bSSFP minus CS_bSSFP, mean ± SD) and Pearson's correlations were 14.8 ± 16.3 (P = 0.31) and r = 0.98 (P < 0.0001) for end-diastolic volume (EDV), 8.4 ± 11.3 (P = 0.54) and r = 0.99 (P < 0.0001) for end-systolic volume (ESV), -0.4 ± 2.5 (P = 0.87) and r = 0.97 (P < 0.0001) for EF, and -0.9 ± 11.8 (P = 0.92) and r = 0.97 (P < 0.0001) for LV mass. Bland-Altman analyses [bias and (limits of agreement)] revealed strong agreement in LVEDV [8.7 ml, (-12.1, 29.6)], LVESV [4.3 ml, (-11.9, 20.6)], LVEF [-0.02%, (-5.37, 5.33)], and myocardial mass [-6.1 g, (-14.7, 26.9)]. Image quality was comparable with a similar mean score (P = 0.42), with a good correlation in image quality observed (r = 0.68, P < 0.0001). Quantitative regional myocardial wall motion demonstrated strong correlation between the sequences (r = 0.87, P < 0.0001). Imaging time was significantly shorter for the CS_bSSFP sequence (1.1 ± 0.5 versus 5.6 ± 1.6 min, P < 0.0001). CONCLUSION: The novel high-resolution cine CS_bSSFP accurately and reliably quantitates LV volumes and mass, shortens acquisition times, and is clinically feasible. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1693-1699.

Gas exchange responses during 6-min walk test in patients with pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: The 6-min walk test (6MWT) is the most widely utilized method of assessing exercise capacity in pulmonary arterial hypertension (PAH). Cardiopulmonary exercise testing has the advantage of providing additional physiological information over 6MWT. The goals of our study were to describe the addition of gas exchange measurements to 6MWT and to determine how these parameters were related to the severity of PAH in three major subgroups of PAH (idiopathic (IPAH), connective tissue disease-related (CTPAH) and congenital heart disease-related (CHPAH)). METHODS: Seventy-six PAH patients (IPAH, n = 28; CTPAH, n = 24; CHPAH, n = 24) completed the 6MWT with simultaneous gas exchange measurements. The 6-min walk distance (6MWD), oxygen uptake ( V ˙ O2 ), carbon dioxide production ( V ˙ CO2 ), oxygen saturation, minute ventilation to carbon dioxide output ( V ˙ E / V ˙ CO2 ) and end-tidal partial pressure for carbon dioxide (PET CO2 ) were compared between subgroups, different functional classes (FCs) and pharmacotherapy. RESULTS: Whilst no significant difference in 6MWT was observed, absolute V ˙ O2 and V ˙ CO2 were higher for IPAH (P < 0.05). Differences were removed when V ˙ O2 and V ˙ CO2 were expressed relative to body mass (i.e. mL/kg/min). CHPAH had the most significant desaturation during 6MWT (CPAH: 73 ± 15%; CTPAH: 90 ± 8%, IPAH: 92 ± 8%, P < 0.01). There was no difference in V ˙ E / V ˙ CO2 and PET CO2 between groups; however, New York Health Association (NYHA) FC II performed better than FC III subjects in 6MWT with lower V ˙ E / V ˙ CO2 and higher end-exercise PET CO2 . Similarly, individuals on more advanced pharmacotherapy (triple therapy vs monotherapy) had poorer gas exchange during exercise. CONCLUSION: Whilst 6MWT and gas exchange did not differentiate between PAH groups, individuals with more severe disease and on more advanced pharmacotherapy had poorer gas exchange during exercise.

Real-time aortic pulse wave velocity measurement during exercise stress testing.

BACKGROUND: Pulse wave velocity (PWV), a measure of arterial stiffness, has been demonstrated to be an independent predictor of adverse cardiovascular outcomes. This can be derived non-invasively using cardiovascular magnetic resonance (CMR). Changes in PWV during exercise may reveal further information on vascular pathology. However, most known CMR methods for quantifying PWV are currently unsuitable for exercise stress testing. METHODS: A velocity-sensitive real-time acquisition and evaluation (RACE) pulse sequence was adapted to provide interleaved acquisition of two locations in the descending aorta (at the level of the pulmonary artery bifurcation and above the renal arteries) at 7.8 ms temporal resolution. An automated method was used to calculate the foot-to-foot transit time of the velocity pulse wave. The RACE method was validated against a standard gated phase contrast (STD) method in flexible tube phantoms using a pulsatile flow pump. The method was applied in 50 healthy volunteers (28 males) aged 22-75 years using a MR-compatible cycle ergometer to achieve moderate work rate (38 ± 22 W, with a 31 ± 12 bpm increase in heart rate) in the supine position. Central pulse pressures were estimated using a MR-compatible brachial device. Scan-rescan reproducibility was evaluated in nine volunteers. RESULTS: Phantom PWV was 22 m/s (STD) vs. 26 ± 5 m/s (RACE) for a butyl rubber tube, and 5.5 vs. 6.1 ± 0.3 m/s for a latex rubber tube. In healthy volunteers PWV increased with age at both rest (R(2) = 0.31 p < 0.001) and exercise (R(2) = 0.40, p < 0.001). PWV was significantly increased at exercise relative to rest (0.71 ± 2.2 m/s, p = 0.04). Scan-rescan reproducibility at rest was -0.21 ± 0.68 m/s (n = 9). CONCLUSIONS: This study demonstrates the validity of CMR in the evaluation of PWV during exercise in healthy subjects. The results support the feasibility of using this method in evaluating of patients with systemic aortic disease.

Assessment and diagnosis of right ventricular failure-retrospection and future directions.

The right ventricle (RV) has a critical role in hemodynamics and right ventricular failure (RVF) often leads to poor clinical outcome. Despite the clinical importance of RVF, its definition and recognition currently rely on patients' symptoms and signs, rather than on objective parameters from quantifying RV dimensions and function. A key challenge is the geometrical complexity of the RV, which often makes it difficult to assess RV function accurately. There are several assessment modalities currently utilized in the clinical settings. Each diagnostic investigation has both advantages and limitations according to its characteristics. The purpose of this review is to reflect on the current diagnostic tools, consider the potential technological advancements and propose how to improve the assessment of right ventricular failure. Advanced technique such as automatic evaluation with artificial intelligence and 3-dimensional assessment for the complex RV structure has a potential to improve RV assessment by increasing accuracy and reproducibility of the measurements. Further, noninvasive assessments for RV-pulmonary artery coupling and right and left ventricular interaction are also warranted to overcome the load-related limitations for the accurate evaluation of RV contractile function. Future studies to cross-validate the advanced technologies in various populations are required.

Relating exercise-induced desaturation and gas-exchange in pulmonary artery hypertension.

We measured pulmonary gas exchange during six minute walk test (6MWT) in patients with idiopathic (IPAH) and congenital heart disease-related pulmonary hypertension (CHDPH), and determined the relationship between the degree of desaturation and changes in minute ventilation to carbon dioxide production V˙EV˙CO2 and end-tidal partial pressure for carbon dioxide (PetCO2) in both groups. Fifty-two patients (IPAH, n = 28; CHDPH, n = 24) completed 6MWT with simultaneous pulmonary gas exchange. Whilst no significant difference in six minute walk distance was observed between groups (IPAH: 529 ± 89; CHDPH: 476 ± 119 m, p = 0.10), oxygen uptake, carbon dioxide production, and minute ventilation were higher in IPAH than CHDPH (p < 0.01). In addition, CHDPH desaturated to a greater extent than IPAH with a lower post-6MWT SPO2 (IPAH: 92.3 ± 7.9; CHDPH: 73.3 ± 14.9%, p < 0.01). The change in SpO2 correlated to the change in V˙E/V˙CO2 (r=-0.44, p = 0.02) and PetCO2 (r = 0.49, p < 0.01) for CHDPH, but not IPAH. The exercise-induced hypoxic stimulus during 6MWT in CHDPH may be associated with an enhanced ventilatory response.

Comparison of effects of losartan and metoprolol on left ventricular and aortic function at rest and during exercise in chronic aortic regurgitation.

Aortic regurgitation (AR) increases the hemodynamic load on both the left ventricle (LV) and the aorta. Vasodilators and beta-blockers both reduce systemic blood pressure, but their relative effects on the LV and aortic function and aortic regurgitant fraction in chronic AR are uncertain. We aimed to compare short-term effects of losartan and metoprolol on LV and aortic function in asymptomatic patients with chronic moderate to severe AR, both at rest and during exercise, using cardiac magnetic resonance (CMR) imaging. 17 chronic AR patients were randomized to 4-6 weeks losartan followed by metoprolol, or vice versa, in a cross-over design. Aortic regurgitant fraction, aortic distensibility, pulse wave velocity and LV function were assessed at rest and after moderate exercise stress (29 ± 7 W, heart rate increase 25 ± 6 bpm) using CMR. Chronic AR patients on metoprolol had a significantly lower mean heart rate, cardiac power index and rate-pressure product, than on losartan (all p < 0.01). However, aortic regurgitant fraction was greater on metoprolol compared to losartan (by 7 ± 11%, p = 0.02). Metoprolol was also associated with a greater reduction in aortic distensibility during exercise than losartan (- 2.4 ± 1.5 × 10-3 vs - 1.7 ± 2.1 × 10-3 mmHg-1 respectively, p = 0.04). End-diastolic volume index was higher on metoprolol than losartan at exercise (difference 6.6 ± 7.8 ml/m2, p < 0.01), as was end-systolic volume index (difference 4.0 ± 5.2 ml/m2, p < 0.01). Losartan and metoprolol have significantly different short-term effects on aortic regurgitation and LV and aortic function in chronic AR. Further research is required to determine the long-term clinical significance of these changes.

Evaluation of a novel sphygmomanometer, which estimates central aortic blood pressure from analysis of brachial artery suprasystolic pressure waves.

BACKGROUND: Central arterial pressure is a better predictor of adverse cardiovascular outcomes than brachial blood pressure, but noninvasive measurement by applanation tonometry is technically demanding. METHOD: Pulsecor R6.5 is a novel device adapted from a standard sphygmomanometer which estimates the central aortic pressure from analysis of low-frequency suprasystolic waveforms at the occluded brachial artery. A physics-based model, which simulates the arterial system using elastic, thin-walled tube elements and Navier-Stokes equations, is used to calculate arterial pressure and flow propagation. To determine the reliability of the device, we compared 94 central systolic pressures estimated by Pulsecor to the simultaneous directly measured central aortic pressures at the time of coronary angiography in 37 individuals. RESULTS: There was good correlation in central SBP between catheter measurements and Pulsecor estimates by either invasive or noninvasive calibration methods (r = 0.99, P < 0.0001 and r = 0.95, P < 0.0001, respectively). The mean difference in central systolic pressure was 2.78 (SD 3.90) mmHg and coefficient of variation was 0.03 when the invasive calibration method was used.When the noninvasive calibration method was used, the mean difference in central systolic pressure was 0.25 (SD 6.31) mmHg and coefficient of variation was 0.05. CONCLUSION: We concluded that Pulsecor R6.5 provides a simple and easy method to noninvasively estimate central SBP, which has highly acceptable accuracy.