Left ventricular underfilling in PAH: A potential indicator for adaptive-to-maladaptive transition.

Pulmonary arterial hypertension (PAH) still remains a life-threatening disorder with poor prognosis. The right ventricle (RV) adapts to the increased afterload by a series of prognostically significant morphological and functional changes, the adaptive nature should also be understood in the context of ventricular interdependence. We hypothesized that left ventricle (LV) underfilling could serve as an important imaging marker for identifying maladaptive changes and predicting clinical outcomes in PAH patients. We prospectively enrolled patients with PAH who underwent both cardiac magnetic resonance and right heart catheterization between October 2013 and December 2020. Patients were categorized into four groups based on their LV and RV mass/volume ratio (M/V). LV M/V was stratified using the normal value (0.7 g/mL for males and 0.6 g/mL for females) to identify patients with LV underfilling (M/V ≥ normal value), while RV M/V was stratified based on the median value. The primary endpoint was all-cause mortality, and the composite endpoints included all-cause mortality and heart failure-related readmissions. A total of 190 PAH patients (53 male, mean age 37 years) were included in this study. Patients with LV underfilling exhibited higher NT-proBNP levels, increased RV mass, larger RV but smaller LV, lower right ventricular ejection fraction, and shorter 6-min walking distance. Patients with LV underfilling had a 2.7-fold higher risk of mortality than those without and LV M/V (hazard ratio [per 0.1 g/mL increase]: 1.271, 95% confidence interval: 1.082-1.494, p = 0.004) was also independent predictors of all-cause mortality. Moreover, patients with low LV M/V had a better prognosis regardless of the level of RV M/V. Thus, LV underfilling is an independent predictor of adverse clinical outcomes in patients with PAH, and it could be an important imaging marker for identifying maladaptive changes in these patients.

Corrected MRI Pulmonary Transit Time for Identification of Combined Precapillary and Postcapillary Pulmonary Hypertension in Patients With Left Heart Disease.

BACKGROUND: The identification of combined precapillary and postcapillary pulmonary hypertension (CpcPH) in patients with pulmonary hypertension (PH) due to left heart disease (LHD) can influence therapy and outcome and is currently based on invasively determined hemodynamic parameters. PURPOSE: To investigate the diagnostic value of MRI-derived corrected pulmonary transit time (PTTc) in PH-LHD sub-grouped according to hemodynamic phenotypes. STUDY TYPE: Prospective observational study. POPULATION: A total of 60 patients with PH-LHD (18 with isolated postcapillary PH [IpcPH] and 42 with CpcPH), and 33 healthy subjects. FIELD STRENGTH/SEQUENCE: A 3.0 T/balanced steady-state free precession cine and gradient echo-train echo planar pulse first-pass perfusion. ASSESSMENT: In patients, right heart catheterization (RHC) and MRI were performed within 30 days. Pulmonary vascular resistance (PVR) was used as the diagnostic "reference standard." The PTTc was calculated as the time interval between the peaks of the biventricular signal-intensity/time curve and corrected for heart rate. PTTc was compared between patient groups and healthy subjects and its relationship to PVR assessed. The diagnostic accuracy of PTTc for distinguishing IpcPH and CpcPH was determined. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, linear and logistic regression analysis, and receiver-operating characteristic curves. Significance level: P < 0.05. RESULTS: PTTc was significantly prolonged in CpcPH compared with IpcPH and normal controls (17.28 ± 7.67 vs. 8.82 ± 2.55 vs. 6.86 ± 2.11 seconds), and in IpcPH compared with normal controls (8.82 ± 2.55 vs. 6.86 ± 2.11 seconds). Prolonged PTTc was significantly associated with increased PVR. Furthermore, PTTc was a significantly independent predictor of CpcPH (odds ratio: 1.395, 95% confidence interval: 1.071-1.816). The area under curve was 0.852 at a cut-off value of 11.61 seconds for PTTc to distinguish between CpcPH and IpcPH (sensitivity 71.43% and specificity 94.12%). DATA CONCLUSION: PTTc may be used to identify CpcPH. Our findings have potential to improve selection for invasive RHC for PH-LHD patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Prognostic Value of Hepatic Native T1 and Extracellular Volume Fraction in Patients with Pulmonary Arterial Hypertension.

Background Right heart failure may lead to impaired liver perfusion and venous congestion, resulting in different extents of liver fibrosis. However, whether hepatic tissue deterioration determined by native T1 mapping and extracellular volume fraction using cardiac magnetic resonance imaging is associated with poor outcomes in patients with pulmonary arterial hypertension remains unclear. Methods and Results A total of 131 participants with pulmonary arterial hypertension (mean age, 36±13 years) and 64 healthy controls (mean age, 44±18) between October 2013 and December 2019 were prospectively enrolled. Hepatic native T1 and extracellular volume fraction values were measured using modified Look-Locker inversion recovery T1 mapping sequences. The primary end point was all-cause mortality; the secondary end point was all-cause mortality and repeat hospitalization attributable to heart failure. Cox regression models and Kaplan-Meier survival analysis were used to identify the association between variables and clinical outcome. During a median follow-up of 34.5 months (interquartile range: 25.3-50.8), hepatic native T1 (hazard ratio per 30-ms increase, 1.22 [95% CI, 1.07-1.39]; P=0.003) and extracellular volume fraction (hazard ratio per 3% increase, 1.18 [95% CI, 1.04-1.34]; P=0.010) values were associated with a higher risk of death. In the multivariate Cox model, hepatic native T1 value (hazard ratio per 30-ms increase, 1.15 [95% CI, 1.04-1.27]; P=0.009) remained as an independent prognostic factor for the secondary end point. Conclusions Hepatic T1 mapping values were predictors of adverse cardiovascular events in participants with pulmonary arterial hypertension and could be novel imaging biomarkers for poor prognosis recognition.

Detection and evaluation of myocardial fibrosis in Eisenmenger syndrome using cardiovascular magnetic resonance late gadolinium enhancement and T1 mapping.

BACKGROUND: Myocardial fibrosis is a common pathophysiological process involved in many cardiovascular diseases. However, limited prior studies suggested no association between focal myocardial fibrosis detected by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and disease severity in Eisenmenger syndrome (ES). This study aimed to explore potential associations between myocardial fibrosis evaluated by the CMR LGE and T1 mapping and risk stratification profiles including exercise tolerance, serum biomarkers, hemodynamics, and right ventricular (RV) function in these patients. METHODS: Forty-five adults with ES and 30 healthy subjects were included. All subjects underwent a contrast-enhanced 3T CMR. Focal replacement fibrosis was visualized on LGE images. The locations of LGE were recorded. After excluding LGE in ventricular insertion point (VIP), ES patients were divided into myocardial LGE-positive (LGE+) and LGE-negative (LGE-) subgroups. Regions of interest in the septal myocardium were manually contoured in the T1 mapping images to determine the diffuse myocardial fibrosis. The relationships between myocardial fibrosis and 6-min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), hematocrit, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), RV/left ventricular end-systolic volume (RV/LV ESV), RV ejection fraction (RVEF), and risk stratification were analyzed. RESULTS: Myocardial LGE (excluding VIP) was common in ES (16/45, 35.6%), and often located in the septum (12/45, 26.7%). The clinical characteristics, hemodynamics, CMR morphology and function, and extracellular volume fraction (ECV) were similar in the LGE+ and LGE- groups (all P > 0.05). ECV was significantly higher in ES patients (28.6 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) and those with LGE- ES (28.3 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) than healthy controls. We found significant correlations between ECV and log NT-pro BNP, hematocrit, mPAP, PVRI, RV/LV ESV, and RVEF (all P < 0.05), and correlations trends between ECV and 6MWT (P = 0.06) in ES patients. An ECV threshold of 29.0% performed well in differentiating patients with high-risk ES from those with intermediate or low risk (area under curve 0.857, P < 0.001). CONCLUSIONS: Myocardial fibrosis is a common feature of ES. ECV may serve as an important imaging marker for ES disease severity.

The Association of Body Mass Index With the Risk of Pulmonary Hypertension in Adults: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUNDS: Findings regarding the association of body mass index (BMI) with pulmonary hypertension (PH) are conflicting, and there is no systematic review and meta-analysis to summarize the results. Therefore, the purpose of this systematic review and meta-analysis is to assess this relationship. METHODS: To detect the relevant articles, PubMed, Scopus, and Google Scholar were searched until February 2021. Included essays were pooled using a random-effect model. Cochrane Q-test and I2-test was applied to assess between-study heterogeneity. RESULTS: Fourteen articles (eight cross-sectional and four cohort studies) were included in the meta-analysis. The meta-analysis of comparing highest vs. lowest BMI categories did not indicate a significant association between BMI and PH (Summary Effect Estimate: 1.59 (95% CI: 0.50, 5.07, I2 = 92.3). Furthermore, The summary risk estimate for a one-unit increment in BMI was 1.01 (95 % CI: 0.99, 1.03), with high heterogeneity, I2 = 73.5 %, P heterogeneity <0.001). Subgroup analysis showed significant positive association between BMI and the risk of PH in studies controlled for cofounders, and studies with higher sample sizes (≥2,000). CONCLUSION: There is no significant association between BMI and risk of pulmonary hypertension. Further studies are required to confirm these findings.