Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects.

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. RESULTS: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = - 0.355 for LV and - 0.318 for RV), and KEiEDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age. CONCLUSION: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Aortic flow is associated with aging and exercise capacity.

Aims: Increased blood flow eccentricity in the aorta has been associated with aortic (AO) pathology, however, its association with exercise capacity has not been investigated. This study aimed to assess the relationships between flow eccentricity parameters derived from 2-dimensional (2D) phase-contrast (PC) cardiovascular magnetic resonance (CMR) imaging and aging and cardiopulmonary exercise test (CPET) in a cohort of healthy subjects. Methods and Results: One hundred and sixty-nine healthy subjects (age 44 ± 13 years, M/F: 96/73) free of cardiovascular disease were recruited in a prospective study (NCT03217240) and underwent CMR, including 2D PC at an orthogonal plane just above the sinotubular junction, and CPET (cycle ergometer) within one week. The following AO flow parameters were derived: AO forward and backward flow indexed to body surface area (FFi, BFi), average flow displacement during systole (FDsavg), late systole (FDlsavg), diastole (FDdavg), systolic retrograde flow (SRF), systolic flow reversal ratio (sFRR), and pulse wave velocity (PWV). Exercise capacity was assessed by peak oxygen uptake (PVO2) from CPET. The mean values of FDsavg, FDlsavg, FDdavg, SRF, sFRR, and PWV were 17 ± 6%, 19 ± 8%, 29 ± 7%, 4.4 ± 4.2 mL, 5.9 ± 5.1%, and 4.3 ± 1.6 m/s, respectively. They all increased with age (r = 0.623, 0.628, 0.353, 0.590, 0.649, 0.598, all P < 0.0001), and decreased with PVO2 (r = -0.302, -0.270, -0.253, -0.149, -0.219, -0.161, all P < 0.05). A stepwise multivariable linear regression analysis using left ventricular ejection fraction (LVEF), FFi, and FDsavg showed an area under the curve of 0.769 in differentiating healthy subjects with high-risk exercise capacity (PVO2 ≤ 14 mL/kg/min). Conclusion: AO flow haemodynamics change with aging and predict exercise capacity. Registration: NCT03217240.

Comparison of Functional Health Status and Health Related Quality of Life Between Adult Patients With Fontan Procedure and Noncongenital Heart Diseases.

To compare functional health status and Health Related Quality of Life (HRQoL) between Fontan and non-congenital heart disease (CHD) patients in an Asian population. Functional health status and HRQoL (New York Heart Association (NYHA) functional class, Duke Activity Status Index (DASI), HeartQol and EQ-5D-5L) were measured. A total of 65 patients (twenty Fontan patients, mean age 28 ± 5; and 45 age-matched non-CHD patients, mean age 33 ± 5) were recruited. After adjustment for age, gender and ethnicity, there were no significant differences in functional health status and HRQoL between groups. In an Asian population, Fontan patients have similar functional health status and Health Related Quality of Life compared to non-CHD patients.

Longitudinal analysis of thoracic aortic expansion in non-syndromic real-world patients.

Remodeling of the thoracic aorta is commonly seen and viewed as a precursor to an aortic aneurysm. However, while aneurysms have been shown to expand at a rate of approximately 1 mm annually, the expansion of the pre-aneurysmal aorta is poorly characterized, especially in relation to age, gender, and aortic size per se. We identified patients that had undergone echocardiography at least twice at a large university medical center. Diagnosis codes, medications, and blood test results were obtained from hospital records. Syndromic patients were excluded (e.g., Marfan's syndrome, bicuspid aortic valve). Final population comprised n = 24,928 patients (median age 61.2 years (inter-quartile range (IQR): 50.6-71.5); 55.8% males) that had undergone a median of 3 echocardiograms (2-4; range 2-27) during a median of 4.0 years (IQR: 2.3-6.2). Hypertension was present in 39.6% of patients and diabetes in 20.7%, median LV ejection fraction was 56.0% (IQR: 41.0-62.0). Aortic size measurements were analyzed in mixed models while clustering on individual patients. Mean expansion was determined for sinus of Valsalva as 1.93 (95% confidence interval; CI95: 1.87-1.99) mm per decade, and for ascending aorta as 1.76 (CI95: 1.70-1.82) mm per decade. Faster expansion was found in males, with larger aortic size, and younger age (p for interaction <0.05 for all). In conclusion, expansion of the thoracic aorta, in real world, non-syndromic patients, is slow and averages <2 mm per decade. This will help to inform management of this large patient group.

Pulmonary Artery Strain Predicts Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Current cardiac magnetic resonance (CMR) imaging in pulmonary arterial hypertension (PAH) focuses on measures of ventricular function and coupling. OBJECTIVES: The purpose of this study was to evaluate pulmonary artery (PA) global longitudinal strain (GLS) as a prognostic marker in patients with PAH. METHODS: The authors included 169 patients with PAH from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) and INITIATE (Integrated computatioNal modelIng of righT heart mechanIcs and blood flow dynAmics in congeniTal hEart disease) registries, and 82 normal controls with similar age and gender distributions. PA GLS was derived from CMR feature tracking. Right ventricular measurements including volumes, ejection fraction, and right ventricular GLS were also derived from CMR. Patients were followed up a median of 34 months with all-cause mortality as the primary endpoint. Other known risk scores were collected, including the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) 2.0 and COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) 2.0 scores. RESULTS: Of 169 patients (mean age: 57 ± 15 years; 80% female), 45 (26.6%) died (median follow-up: 34 months). Mean PA GLS was 23% ± 6% in normal controls and 10% ± 5% in patients with PAH (P < 0.0001). Patients with PA GLS <9% had a higher risk of mortality than those with PA GLS ≥9% (P < 0.001), and this was an independent predictor of mortality in PAH on multivariable analysis after adjustment for known risk factors (HR: 2.93; P = 0.010). Finally, in patients with PAH, PA GLS provided incremental prognostic value over the REVEAL 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.030) and COMPERA 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.048). CONCLUSIONS: PA GLS confers incremental prognostic utility over the established risk scores for identifying patients with PAH at higher risk of death, who may be targeted for closer monitoring and/or intensified therapy.

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension.

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. METHODS: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. RESULTS: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. CONCLUSION: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. METHODS: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. RESULTS: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEiEDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEiEDV were independent predictors of RV remodelling index. CONCLUSIONS: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

Age- and Sex-Specific Changes in CMR Feature Tracking-Based Right Atrial and Ventricular Functional Parameters in Healthy Asians.

Cardiovascular magnetic resonance (CMR) is the reference standard for non-invasive assessment of right-sided heart function. Recent advances in CMR post-processing facilitate quantification of tricuspid annular (TA) dynamics and longitudinal strains of the right ventricle (RV) and right atrium (RA). We aimed to determine age- and sex-specific changes in CMR-derived TA dynamics, and RV and RA functional parameters in healthy Asian adults. We studied 360 healthy subjects aged 21-79 years, with 30 men and 30 women in each of the six age groups. Functional parameters of RV and RA were measured on standard four-chamber cine CMR using fast feature tracking: (1) TA peak velocities (systolic velocity S', early diastolic velocity E', late diastolic velocity A') and TA plane systolic excursion (TAPSE); (2) RV global longitudinal strain (GLS) and strain rates; and (3) RA phasic longitudinal strains and strain rates. S' and TAPSE exhibited negative correlations with age. RV GLS was significantly higher in females than in males but not associated with age in both sexes. Females had similar E', lower A', and higher E'/A' ratios compared to males. Positive associations of E' and E'/A', and negative association of A' with age were observed in both sexes. Females had higher RA reservoir and conduit strains compared to males. There were significantly negative and positive associations between RA conduit and booster strains, respectively, with age. Age- and sex-specific reference ranges were established, and associations revealed, for fast CMR feature tracking parameters of right heart function in a large normal Asian population.

Impact of age, sex and ethnicity on intra-cardiac flow components and left ventricular kinetic energy derived from 4D flow CMR.

BACKGROUND: Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) allows quantification of left ventricular (LV) blood flow. We aimed to 1) establish reference ranges for 4D flow CMR-derived LV relative flow components and kinetic energy parameters indexed to end-diastolic volume (KEiEDV) among healthy Asian subjects, 2) assess effects of age and sex on these parameters, and 3) compare these parameters between Asian and Caucasian subjects. METHODS: 74 healthy Asian subjects underwent cine and 4D flow CMR. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (LV global, peak systolic, systolic, diastolic, peak E-wave, peak A-wave) were analyzed. Sex- and age-specific reference ranges were reported. RESULTS: Relative flow components and systolic phase KEiEDV did not vary with age. Women had higher retained inflow and peak E-wave KEiEDV, lower residual volume, peak systolic and systolic KEiEDV than men. Peak A-wave KEiEDV increased significantly (r = 0.474) whereas peak E-wave KEiEDV (r = -0.458) and E-wave/A-wave ratio (r = -0.528) decreased with age. A sub-population (n = 44) was compared with 44 sex- and age-matched Caucasian subjects: no significant group differences were observed for all 4D flow CMR parameters. CONCLUSION: Asian sex- and age-specific 4D flow CMR reference ranges were established. Sex differences in retained inflow, residual volume, peak systolic, systolic KEiEDV and peak E-wave KEiEDV were observed. Ageing influenced diastolic KEiEDV but not systolic phase KEiEDV or relative flow components. All studied parameters were similar between sex- and age-matched Asian and Caucasian subjects, implying generalizability of the ranges.

Cardiovascular magnetic resonance-assessed fast global longitudinal strain parameters add diagnostic and prognostic insights in right ventricular volume and pressure loading disease conditions.

BACKGROUND: Parameters of myocardial deformation may provide improved insights into right ventricular (RV) dysfunction. We quantified RV longitudinal myocardial function using a fast, semi-automated method and investigated its diagnostic and prognostic values in patients with repaired tetralogy of Fallot (rTOF) and pulmonary arterial hypertension (PAH), who respectively exemplify patients with RV volume and pressure overload conditions. METHODS: The study enrolled 150 patients (rTOF, n = 75; PAH, n = 75) and 75 healthy controls. RV parameters of interest were fast global longitudinal strain (GLS) and strain rates during systole (GLSRs), early diastole (GLSRe) and late diastole (GLSRa), obtained by tracking the distance from the medial and lateral tricuspid valve insertions to the RV epicardial apex on cine cardiovascular magnetic resonance (CMR). RESULTS: The RV fast GLS exhibited good agreement with strain values obtained by conventional feature tracking approach (bias - 4.9%, error limits (± 2·standard deviation) ± 4.3%) with fast GLS achieving greater reproducibility and requiring reduced analysis time. Mean RV fast GLS was reduced in PAH and rTOF groups compared to healthy controls (PAH < rTOF < healthy controls: 15.1 ± 4.9 < 19.3 ± 2.4 < 24.4 ± 3.0%, all P < 0.001 in pairwise comparisons). In rTOF patients, RV fast GLS was significantly associated with metabolic equivalents, peak oxygen consumption (PVO2) and percentage of predicted PVO2 achieved during cardiopulmonary exercise testing. Lower RV fast GLS was associated with subnormal exercise capacity in rTOF (area under the curve (AUC) = 0.822, sensitivity = 72%, specificity = 91%, cut-off = 19.3%). In PAH patients, reduced RV fast GLS was associated with RV decompensated hemodynamics (AUC = 0.717, sensitivity = 75%, specificity = 58%, cut-off = 14.6%) and higher risk of clinical worsening (AUC = 0.808, sensitivity = 79%, specificity = 70 %, cut-off = 16.0%). CONCLUSIONS: Quantitative RV fast strain and strain rate parameters assessed from CMR identify abnormalities of RV function in rTOF and PAH and are predictive of exercise capacity, RV decompensation and clinical risks in these patients. Trial registry Clinicaltrials.gov: NCT03217240.

Clinical Updates on the Diagnosis and Management of Chronic Thromboembolic Pulmonary Hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a known sequela after acute pulmonary embolism (PE). It is a debilitating disease, and potentially fatal if left untreated. This review provides a clinically relevant overview of the disease and discusses the usefulness and limitations of the various investigational and treatment options. METHODS: A PubMed search on articles relevant to PE, pulmonary hypertension, CTEPH, pulmonary endarterectomy, and balloon pulmonary angioplasty were performed. A total of 68 articles were found to be relevant and were reviewed. RESULTS: CTEPH occurs as a result of non-resolution of thrombotic material, with subsequent fibrosis and scarring of the pulmonary arteries. Risk factors have been identified, but the underlying mechanisms have yet to be fully elucidated. The cardinal symptom of CTEPH is dyspnoea on exertion, but the diagnosis is often challenging due to lack of awareness. The ventilation/perfusion scan is recommended for screening for CTEPH, with other modalities (eg. dual energy computed tomography pulmonary angiography) also being utilised in expert centres. Conventional pulmonary angiography with right heart catheterisation is important in the final diagnosis of CTEPH. CONCLUSION: Operability assessment by a multidisciplinary team is crucial for the management of CTEPH, as pulmonary endarterectomy (PEA) remains the guideline recommended treatment and has the best chance of cure. For inoperable patients or those with residual disease post-PEA, medical therapy or balloon pulmonary angioplasty are potential treatment options.

Three-dimensional biventricular strains in pulmonary arterial hypertension patients using hyperelastic warping.

BACKGROUND AND OBJECTIVE: Evaluation of biventricular function is an essential component of clinical management in pulmonary arterial hypertension (PAH). This study aims to examine the utility of biventricular strains derived from a model-to-image registration technique in PAH patients in comparison to age- and gender-matched normal controls. METHODS: A three-dimensional (3D) model was reconstructed from cine short- and long-axis cardiac magnetic resonance (CMR) images and subsequently partitioned into right ventricle (RV), left ventricle (LV) and septum. The hyperelastic warping method was used to register the meshed biventricular finite element model throughout the cardiac cycle and obtain the corresponding biventricular circumferential, longitudinal and radial strains. RESULTS: Intra- and inter-observer reproducibility of biventricular strains was excellent with all intra-class correlation coefficients > 0.84. 3D biventricular longitudinal, circumferential and radial strains for RV, LV and septum were significantly decreased in PAH patients compared with controls. Receiver operating characteristic (ROC) analysis showed that the 3D biventricular strains were better early markers (Area under the ROC curve = 0.96 for RV longitudinal strain) of ventricular dysfunction than conventional parameters such as two-dimensional strains and ejection fraction. CONCLUSIONS: Our highly reproducible methodology holds potential for extending CMR imaging to characterize 3D biventricular strains, eventually leading to deeper understanding of biventricular mechanics in PAH.

TGA With Interarterial Course and Athletes Heart: A Diagnostic Dilemma Answered by Stress CMR.

We report a case of coronary artery compression and athlete's heart in a patient with a history of transposition of the great arteries. We present the diagnostic dilemmas and demonstrate the use of cardiac magnetic resonance imaging and cycle-ergometer stress cardiac magnetic resonance in the management of our patient. (Level of Difficulty: Intermediate.).

Patient-Specific Computational Analysis of Hemodynamics and Wall Mechanics and Their Interactions in Pulmonary Arterial Hypertension.

Vascular wall stiffness and hemodynamic parameters are potential biomechanical markers for detecting pulmonary arterial hypertension (PAH). Previous computational analyses, however, have not considered the interaction between blood flow and wall deformation. Here, we applied an established computational framework that utilizes patient-specific measurements of hemodynamics and wall deformation to analyze the coupled fluid-vessel wall interaction in the proximal pulmonary arteries (PA) of six PAH patients and five control subjects. Specifically, we quantified the linearized stiffness (E), relative area change (RAC), diastolic diameter (D), regurgitant flow, and time-averaged wall shear stress (TAWSS) of the proximal PA, as well as the total arterial resistance (R t ) and compliance (C t ) at the distal pulmonary vasculature. Results found that the average proximal PA was stiffer [median: 297 kPa, interquartile range (IQR): 202 kPa vs. median: 75 kPa, IQR: 5 kPa; P = 0.007] with a larger diameter (median: 32 mm, IQR: 5.25 mm vs. median: 25 mm, IQR: 2 mm; P = 0.015) and a reduced RAC (median: 0.22, IQR: 0.10 vs. median: 0.42, IQR: 0.04; P = 0.004) in PAH compared to our control group. Also, higher total resistance (R t ; median: 6.89 mmHg × min/l, IQR: 2.16 mmHg × min/l vs. median: 3.99 mmHg × min/l, IQR: 1.15 mmHg × min/l; P = 0.002) and lower total compliance (C t ; median: 0.13 ml/mmHg, IQR: 0.15 ml/mmHg vs. median: 0.85 ml/mmHg, IQR: 0.51 ml/mmHg; P = 0.041) were observed in the PAH group. Furthermore, lower TAWSS values were seen at the main PA arteries (MPAs) of PAH patients (median: 0.81 Pa, IQR: 0.47 Pa vs. median: 1.56 Pa, IQR: 0.89 Pa; P = 0.026) compared to controls. Correlation analysis within the PAH group found that E was directly correlated to the PA regurgitant flow (r = 0.84, P = 0.018) and inversely related to TAWSS (r = -0.72, P = 0.051). Results suggest that the estimated elastic modulus E may be closely related to PAH hemodynamic changes in pulmonary arteries.

Mortality and hospitalization outcomes of interstitial lung disease and pulmonary hypertension in the Singapore systemic sclerosis cohort.

OBJECTIVES: We compared mortality and hospitalization rates in four groups of patients with systemic sclerosis (SSc) [isolated pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD), concomitant ILD-pulmonary hypertension (PH), and no/mild pulmonary involvement]. METHODS: In the Systemic Sclerosis Cohort Singapore (SCORE), ILD was diagnosed by HRCT and significant ILD was defined by forced vital capacity <70% predicted. Patients were classified as PAH if echocardiographic systolic pulmonary artery pressure (sPAP) ≥50 mmHg or right heart catheterization (RHC) mean PAP ≥25 mmHg. Multivariable regression analyses were performed to determine factors associated with mortality and hospital admissions per year. Cox proportional hazard model was used to analyze survival. RESULTS: Of 490 SSc patients, 50 patients had PAH, 92 patients had ILD and 43 patients had ILD-PH. Of 93 patients with PAH or ILD-PH, 56 were based on echocardiography and 37 on RHC. Patients with ILD-PH (HR 3.77, 95% CI: 2.05-6.93) had the highest risk of death, followed by PAH (HR 3.03, 95% CI: 1.60-5.76) and ILD (HR 1.84, 95% CI: 1.04-3.28). After adjustment for confounders, PAH (HR 2.39, 95% CI: 1.13-5.07) remained independently associated with mortality, but not ILD-PH or ILD. Other factors associated with mortality were male gender, age at SSc diagnosis, malabsorption and digital ulcer/ gangrene. Increased hospitalization rate was associated with renal crisis, right heart failure and PAH medications, but not SSc groups. CONCLUSION: PAH is an independent risk factor of mortality in SSc. Increased hospitalization rate was not associated with SSc groups. Other factors associated with increased mortality and hospital admissions were identified.

Computational quantification of patient-specific changes in ventricular dynamics associated with pulmonary hypertension.

Pulmonary arterial hypertension (PAH) causes an increase in the mechanical loading imposed on the right ventricle (RV) that results in progressive changes to its mechanics and function. Here, we quantify the mechanical changes associated with PAH by assimilating clinical data consisting of reconstructed three-dimensional geometry, pressure, and volume waveforms, as well as regional strains measured in patients with PAH (n = 12) and controls (n = 6) within a computational modeling framework of the ventricles. Modeling parameters reflecting regional passive stiffness and load-independent contractility as indexed by the tissue active tension were optimized so that simulation results matched the measurements. The optimized parameters were compared with clinical metrics to find usable indicators associated with the underlying mechanical changes. Peak contractility of the RV free wall (RVFW) γRVFW,max was found to be strongly correlated and had an inverse relationship with the RV and left ventricle (LV) end-diastolic volume ratio (i.e., RVEDV/LVEDV) (RVEDV/LVEDV)+ 0.44, R2 = 0.77). Correlation with RV ejection fraction (R2 = 0.50) and end-diastolic volume index (R2 = 0.40) were comparatively weaker. Patients with with RVEDV/LVEDV > 1.5 had 25% lower γRVFW,max (P < 0.05) than that of the control. On average, RVFW passive stiffness progressively increased with the degree of remodeling as indexed by RVEDV/LVEDV. These results suggest a mechanical basis of using RVEDV/LVEDV as a clinical index for delineating disease severity and estimating RVFW contractility in patients with PAH.NEW & NOTEWORTHY This article presents patient-specific data assimilation of a patient cohort and physical description of clinical observations.

Impaired Cardiovascular Magnetic Resonance-Derived Rapid Semiautomated Right Atrial Longitudinal Strain Is Associated With Decompensated Hemodynamics in Pulmonary Arterial Hypertension.

Background The transition of right ventricle (RV) from a compensated to decompensated state contributes to survival in pulmonary arterial hypertension (PAH). This study investigates the significance of right atrial (RA) dysfunction on disease progression in PAH. Methods Eighty patients with PAH, including 58 with hemodynamically compensated RV function (PAH-C) and 22 with decompensated RV function (PAH-D), were compared with 80 age-matched and sex-matched normal controls. RA longitudinal strain and strain rate (SR) parameters corresponding to reservoir (total strain ε s and strain rate SRs), conduit (passive strain ε e and strain rate SRe), and booster pump (active strain ε a and strain rate SRa) phases were derived by a rapid semiautomated method on cine cardiovascular magnetic resonance. Results In PAH compared with controls, significantly reduced RA strains and SRs were observed. Among patients with PAH, PAH-D had significantly impaired RA strains and SRs compared with PAH-C. RA total strain and passive strain were the best parameters for differentiating PAH-D from PAH-C. Lower RA strain correlated with increased RA pressure ( r=-0.57; P<0.0001), RV volume ( r=-0.37; P=0.002) and biomarker ( r=-0.53; P<0.0001), impaired RV function ( r=0.46-0.72; P<0.0001), and lower exercise capacity ( r=0.41; P<0.0001). Reduced RA strains were significantly associated with higher risk of clinical worsening in PAH. RA passive strain was the best predictor of a composite adverse event end point (Harrell's C statistic,0.75; hazard ratio,0.84; P=0.019) compared with other conventional RA and RV functional measurements. Conclusions RA phasic functions are impaired in PAH. Among patients with PAH, impaired RA strains reflect RV decompensation and higher risks and predict adverse clinical outcomes. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT02790918.

Elevated Right Atrial Pressure Associated with Alteration of Left Ventricular Contractility and Ventricular-Arterial Coupling in Pulmonary Artery Hypertension.

Pulmonary artery hypertension (PAH) is a progressive disorder which leads to heart failure and death. Development of dilated right ventricle (RV), progressive RV dysfunction and increased right atrial (RA) pressure make the RV transition from a compensated to a decompensated phase and eventually leads to heart failure. However, the relationship between elevated RA pressure and left ventricular contractility and ventricular arterial coupling (VAC) has not been well studied. 36 patients were recruited and underwent both right heart catheterization (RHC) and cardiac magnetic resonance (CMR). Left ventricular (LV) pressure-volume loops were reconstructed from RHC and CMR. LV contractility was assessed by end-systolic elastance (Ees) using single-beat method and arterial elastance (Ea) was estimated as the ratio of end-systolic pressure and stroke volume (SV). The VAC was calculated as the ratio of Ees and Ea (i.e. Ees/Ea). The results demonstrated a nonlinear relationship between RA pressure and Ees, RA pressure and VAC. Ees increased when RA pressure increased to 7 mmHg and then decreased when RA pressure exceeded 7 mmHg. Ees were 2.79 ± 1.61 mmHg/ml, 4.27 ±1 33 mmHg/ml, 2.69 ± 0.89 mmHg/ml and 2.36± 1.10 mmHg/ml at ascending quartiles of RA pressure, respectively (quartile 1: RAP≤5 mmHg; quartile 2: 5<; RAP≤7 mmHg; quartile 3: 7<; RAP 10 mmHg and quartile 4: RAP>10 mmHg). Similarly, VAC were 1.36 ± 0.61, 1.93±0.86, 1.16 ± 0.55 and 0.95± 0.27 the four quartiles (both ANOVA P <; 0.05). We found that there was a nonlinear relationship between RA pressure and LV contractility, and between RA pressure and ventricular-arterial coupling. A cut-off value of 7 mmHg of RAP may indicate a decompensated LV hemodynamics.