Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.

BACKGROUND: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. METHODS: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included. RESULTS: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents. CONCLUSIONS: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

Artificial Intelligence framework with traditional computer vision and deep learning approaches for optimal automatic segmentation of left ventricle with scar.

Automatic segmentation of the cardiac left ventricle with scars remains a challenging and clinically significant task, as it is essential for patient diagnosis and treatment pathways. This study aimed to develop a novel framework and cost function to achieve optimal automatic segmentation of the left ventricle with scars using LGE-MRI images. To ensure the generalization of the framework, an unbiased validation protocol was established using out-of-distribution (OOD) internal and external validation cohorts, and intra-observation and inter-observer variability ground truths. The framework employs a combination of traditional computer vision techniques and deep learning, to achieve optimal segmentation results. The traditional approach uses multi-atlas techniques, active contours, and k-means methods, while the deep learning approach utilizes various deep learning techniques and networks. The study found that the traditional computer vision technique delivered more accurate results than deep learning, except in cases where there was breath misalignment error. The optimal solution of the framework achieved robust and generalized results with Dice scores of 82.8 ± 6.4% and 72.1 ± 4.6% in the internal and external OOD cohorts, respectively. The developed framework offers a high-performance solution for automatic segmentation of the left ventricle with scars using LGE-MRI. Unlike existing state-of-the-art approaches, it achieves unbiased results across different hospitals and vendors without the need for training or tuning in hospital cohorts. This framework offers a valuable tool for experts to accomplish the task of fully automatic segmentation of the left ventricle with scars based on a single-modality cardiac scan.

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.

Quantifying Myocardial Blood Flow and Resistance Using 4D-Flow Cardiac Magnetic Resonance Imaging.

Background: Ischaemia with nonobstructive coronary arteries is most commonly caused by coronary microvascular dysfunction but remains difficult to diagnose without invasive testing. Myocardial blood flow (MBF) can be quantified noninvasively on stress perfusion cardiac magnetic resonance (CMR) or positron emission tomography but neither is routinely used in clinical practice due to practical and technical constraints. Quantification of coronary sinus (CS) flow may represent a simpler method for CMR MBF quantification. 4D flow CMR offers comprehensive intracardiac and transvalvular flow quantification. However, it is feasibility to quantify MBF remains unknown. Methods: Patients with acute myocardial infarction (MI) and healthy volunteers underwent CMR. The CS contours were traced from the 2-chamber view. A reformatted phase contrast plane was generated through the CS, and flow was quantified using 4D flow CMR over the cardiac cycle and normalised for myocardial mass. MBF and resistance (MyoR) was determined in ten healthy volunteers, ten patients with myocardial infarction (MI) without microvascular obstruction (MVO), and ten with known MVO. Results: MBF was quantified in all 30 subjects. MBF was highest in healthy controls (123.8 ± 48.4 mL/min), significantly lower in those with MI (85.7 ± 30.5 mL/min), and even lower in those with MI and MVO (67.9 ± 29.2 mL/min/) (P < 0.01 for both differences). Compared with healthy controls, MyoR was higher in those with MI and even higher in those with MI and MVO (0.79 (±0.35) versus 1.10 (±0.50) versus 1.50 (±0.69), P=0.02). Conclusions: MBF and MyoR can be quantified from 4D flow CMR. Resting MBF was reduced in patients with MI and MVO.

Automatic development of 3D anatomical models of border zone and core scar regions in the left ventricle.

Patients with myocardial infarction are at elevated risk of sudden cardiac death, and scar tissue arising from infarction is known to play a role. The accurate identification of scars therefore is crucial for risk assessment, quantification and guiding interventions. Typically, core scars and grey peripheral zones are identified by radiologists and clinicians based on cardiac late gadolinium enhancement magnetic resonance images (LGE-MRI). Scar regions from LGE-MRI vary in size, shape, heterogeneity, artifacts, and image resolution. Thus, manual segmentation is time consuming, and influenced by the observer's experience (bias effect). We propose a fully automatic framework that develops 3D anatomical models of the left ventricle with border zone and core scar regions that are free from bias effect. Our myocardium (SOCRATIS), border scar and core scar (BZ-SOCRATIS) segmentation pipelines were evaluated using internal and external validation datasets. The automatic myocardium segmentation framework performed a Dice score of 81.9% and 70.0% in the internal and external validation dataset. The automatic scar segmentation pipeline achieved a Dice score of 60.9% for the core scar segmentation and 43.7% for the border zone scar segmentation in the internal dataset and in the external dataset a Dice score of 44.2% for the core scar segmentation and 54.8% for the border scar segmentation respectively. To the best of our knowledge, this is the first study outlining a fully automatic framework to develop 3D anatomical models of the left ventricle with border zone and core scar regions. Our method exhibits high performance without the need for training or tuning in an unseen cohort (unsupervised).

Quantitative CT Evaluation of Small Pulmonary Vessels Has Functional and Prognostic Value in Pulmonary Hypertension.

Background The in vivo relationship between peel pulmonary vessels, small pulmonary vessels, and pulmonary hypertension (PH) is not fully understood. Purpose To quantitatively assess peel pulmonary vessel volumes (PPVVs) and small pulmonary vessel volumes (SPVVs) as estimated from CT pulmonary angiography (CTPA) in different subtypes of PH compared with controls, their relationship to pulmonary function and right heart catheter metrics, and their prognostic value. Materials and Methods In this retrospective single-center study performed from January 2008 to February 2018, quantitative CTPA analysis of total SPVV (TSPVV) (0.4- to 2-mm vessel diameter) and PPVV (within 15, 30, and 45 mm from the lung surface) was performed. Results A total of 1823 patients (mean age, 69 years ± 13 [SD]; 1192 women [65%]) were retrospectively analyzed; 1593 patients with PH (mean pulmonary arterial pressure [mPAP], 43 mmHg ± 13 [SD]) were compared with 230 patient controls (mPAP, 19 mm Hg ± 3). The mean vessel volumes in pulmonary peels at 15-, 30-, and 45-mm depths were higher in pulmonary arterial hypertension (PAH) and PH secondary to lung disease compared with chronic thromboembolic PH (45-mm peel, mean difference: 6.4 mL [95% CI: 1, 11] [P < .001] vs 6.8 mL [95% CI: 1, 12] [P = .01]). Mean small vessel volumes at a diameter of less than 2 mm were lower in PAH and PH associated with left heart disease compared with controls (1.6-mm vessels, mean difference: -4.3 mL [95% CI: -8, -0.1] [P = .03] vs -6.8 mL [95% CI: -11, -2] [P < .001]). In patients with PH, the most significant positive correlation was noted with forced vital capacity percentage predicted (r = 0.30-0.40 [all P < .001] for TSPVVs and r = 0.21-0.25 [all P < .001] for PPVVs). Conclusion The volume of pulmonary small vessels is reduced in pulmonary arterial hypertension and pulmonary hypertension (PH) associated with left heart disease, with similar volume of peel vessels compared with controls. For chronic thromboembolic PH, the volume of peel vessels is reduced. In PH, small pulmonary vessel volume is associated with pulmonary function tests. Clinical trial registration no. NCT02565030 Published under a CC BY 4.0 license Online supplemental material is available for this article.

Validation of Artificial Intelligence Cardiac MRI Measurements: Relationship to Heart Catheterization and Mortality Prediction.

Background Cardiac MRI measurements have diagnostic and prognostic value in the evaluation of cardiopulmonary disease. Artificial intelligence approaches to automate cardiac MRI segmentation are emerging but require clinical testing. Purpose To develop and evaluate a deep learning tool for quantitative evaluation of cardiac MRI functional studies and assess its use for prognosis in patients suspected of having pulmonary hypertension. Materials and Methods A retrospective multicenter and multivendor data set was used to develop a deep learning-based cardiac MRI contouring model using a cohort of patients suspected of having cardiopulmonary disease from multiple pathologic causes. Correlation with same-day right heart catheterization (RHC) and scan-rescan repeatability was assessed in prospectively recruited participants. Prognostic impact was assessed using Cox proportional hazard regression analysis of 3487 patients from the ASPIRE (Assessing the Severity of Pulmonary Hypertension In a Pulmonary Hypertension Referral Centre) registry, including a subset of 920 patients with pulmonary arterial hypertension. The generalizability of the automatic assessment was evaluated in 40 multivendor studies from 32 centers. Results The training data set included 539 patients (mean age, 54 years ± 20 [SD]; 315 women). Automatic cardiac MRI measurements were better correlated with RHC parameters than were manual measurements, including left ventricular stroke volume (r = 0.72 vs 0.68; P = .03). Interstudy repeatability of cardiac MRI measurements was high for all automatic measurements (intraclass correlation coefficient range, 0.79-0.99) and similarly repeatable to manual measurements (all paired t test P > .05). Automated right ventricle and left ventricle cardiac MRI measurements were associated with mortality in patients suspected of having pulmonary hypertension. Conclusion An automatic cardiac MRI measurement approach was developed and tested in a large cohort of patients, including a broad spectrum of right ventricular and left ventricular conditions, with internal and external testing. Fully automatic cardiac MRI assessment correlated strongly with invasive hemodynamics, had prognostic value, were highly repeatable, and showed excellent generalizability. Clinical trial registration no. NCT03841344 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh and Lima in this issue. An earlier incorrect version appeared online. This article was corrected on June 27, 2022.

CMR Measures of Left Atrial Volume Index and Right Ventricular Function Have Prognostic Value in Chronic Thromboembolic Pulmonary Hypertension.

Providing prognostic information is important when counseling patients and planning treatment strategies in chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to assess the prognostic value of gold standard imaging of cardiac structure and function using cardiac magnetic resonance imaging (CMR) in CTEPH. Consecutive treatment-naive patients with CTEPH who underwent right heart catheterization and CMR between 2011 and 2017 were identified from the ASPIRE (Assessing-the-Specturm-of-Pulmonary-hypertensIon-at-a-REferral-center) registry. CMR metrics were corrected for age and sex where appropriate. Univariate and multivariate regression models were generated to assess the prognostic ability of CMR metrics in CTEPH. Three hundred and seventy-five patients (mean+/-standard deviation: age 64+/-14 years, 49% female) were identified and 181 (48%) had pulmonary endarterectomy (PEA). For all patients with CTEPH, left-ventricular-stroke-volume-index-%predicted (LVSVI%predicted) (p = 0.040), left-atrial-volume-index (LAVI) (p = 0.030), the presence of comorbidities, incremental shuttle walking test distance (ISWD), mixed venous oxygen saturation and undergoing PEA were independent predictors of mortality at multivariate analysis. In patients undergoing PEA, LAVI (p < 0.010), ISWD and comorbidities and in patients not undergoing surgery, right-ventricular-ejection-fraction-%predicted (RVEF%pred) (p = 0.040), age and ISWD were independent predictors of mortality. CMR metrics reflecting cardiac function and left heart disease have prognostic value in CTEPH. In those undergoing PEA, LAVI predicts outcome whereas in patients not undergoing PEA RVEF%pred predicts outcome. This study highlights the prognostic value of imaging cardiac structure and function in CTEPH and the importance of considering left heart disease in patients considered for PEA.

Semi-automatic thresholding of RV trabeculation improves repeatability and diagnostic value in suspected pulmonary hypertension.

Objectives: Right ventricle (RV) mass is an imaging biomarker of mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR). Some methods of RV mass measurement on cardiac MRI (CMR) exclude RV trabeculation. This study assessed the reproducibility of measurement methods and evaluated whether the inclusion of trabeculation in RV mass affects diagnostic accuracy in suspected pulmonary hypertension (PH). Materials and methods: Two populations were enrolled prospectively. (i) A total of 144 patients with suspected PH who underwent CMR followed by right heart catheterization (RHC). Total RV mass (including trabeculation) and compacted RV mass (excluding trabeculation) were measured on the end-diastolic CMR images using both semi-automated pixel-intensity-based thresholding and manual contouring techniques. (ii) A total of 15 healthy volunteers and 15 patients with known PH. Interobserver agreement and scan-scan reproducibility were evaluated for RV mass measurements using the semi-automated thresholding and manual contouring techniques. Results: Total RV mass correlated more strongly with MPAP and PVR (r = 0.59 and 0.63) than compacted RV mass (r = 0.25 and 0.38). Using a diagnostic threshold of MPAP ≥ 25 mmHg, ROC analysis showed better performance for total RV mass (AUC 0.77 and 0.81) compared to compacted RV mass (AUC 0.61 and 0.66) when both parameters were indexed for LV mass. Semi-automated thresholding was twice as fast as manual contouring (p < 0.001). Conclusion: Using a semi-automated thresholding technique, inclusion of trabecular mass and indexing RV mass for LV mass (ventricular mass index), improves the diagnostic accuracy of CMR measurements in suspected PH.

Left ventricular blood flow kinetic energy is associated with the six-minute walk test and left ventricular remodelling post valvular intervention in aortic stenosis.

BACKGROUND: Left ventricular (LV) kinetic energy (KE) assessment by four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) may offer incremental value over routine assessment in aortic stenosis (AS). The main objective of this study is to investigate the LV KE in patients with AS before and after the valve intervention. In addition, this study aimed to investigate if LV KE offers incremental value for its association to the six-minute walk test (6MWT) or LV remodelling post-intervention. METHODS: We recruited 18 patients with severe AS. All patients underwent transthoracic echocardiography for mean pressure gradient (mPG), CMR including 4D flow and 6MWT. Patients were invited for post-valve intervention follow-up CMR at 3 months and twelve patients returned for follow-up CMR. KE assessment of LV blood flow and the components (direct, delayed, retained and residual) were carried out for all cases. LV KE parameters were normalised to LV end-diastolic volume (LVEDV). RESULTS: For LV blood flow KE assessment, the metrics including time delay (TD) for peak E-wave from base to mid-ventricle (14±48 vs. 2.5±9.75 ms, P=0.04), direct (4.91±5.07 vs. 1.86±1.72 µJ, P=0.01) and delayed (2.46±3.13 vs. 1.38±1.15 µJ, P=0.03) components of LV blood flow demonstrated a significant change between pre- and post-valve intervention. Only LV KEiEDV (r=-0.53, P<0.01), diastolic KEiEDV (r=-0.53, P<0.01) and Ewave KEiEDV (r=-0.38, P=0.04) demonstrated association to the 6MWT. However, Pre-operative LV KEiEDV (r=0.67, P=0.02) demonstrated association to LV remodelling post valve intervention. CONCLUSIONS: LV blood flow KE is associated with 6MWT and LV remodelling in patients with AS. LV KE assessment provides incremental value over routine LV function and pressure gradient (PG) assessment in AS.

Patterns of thromboembolic pulmonary vascular disease in COVID-19.

SARS-CoV-2 (COVID-19) is associated with increased thrombosis. Here, we demonstrate patterns of pulmonary vascular disease in COVID-19 including classical acute pulmonary embolism and subsegmental perfusion defects in the absence of acute pulmonary embolism suggestive of microvascular thrombosis.

Standard and emerging CMR methods for mitral regurgitation quantification.

BACKGROUND: There are several methods to quantify mitral regurgitation (MR) by cardiovascular magnetic resonance (CMR). The interoperability of these methods and their reproducibility remains undetermined. OBJECTIVE: To determine the agreement and reproducibility of different MR quantification methods by CMR across all aetiologies. METHODS: Thirty-five patients with MR were recruited (primary MR = 12, secondary MR = 10 and MVR = 13). Patients underwent CMR, including cines and four-dimensional flow (4D flow). Four methods were evaluated: MRStandard (left ventricular stroke volume - aortic forward flow by phase contrast), MRLVRV (left ventricular stroke volume - right ventricular stroke volume), MRJet (direct jet quantification by 4D flow) and MRMVAV (mitral forward flow by 4D flow - aortic forward flow by 4D flow). For all cases and MR types, 520 MR volumes were recorded by these 4 methods for intra-/inter-observer tests. RESULTS: In primary MR, MRMVAV and MRLVRV were comparable to MRStandard (P > 0.05). MRJet resulted in significantly higher MR volumes when compared to MRStandard (P < 0.05) In secondary MR and MVR cases, all methods were comparable. In intra-observer tests, MRMVAV demonstrated least bias with best limits of agreement (bias = -0.1 ml, -8 ml to 7.8 ml, P = 0.9) and best concordance correlation coefficient (CCC = 0.96, P < 0.01). In inter-observer tests, for primary MR and MVR, least bias and highest CCC were observed for MRMVAV. For secondary MR, bias was lowest for MRJet (-0.1 ml, PNS). CONCLUSION: CMR methods of MR quantification demonstrate agreement in secondary MR and MVR. In primary MR, this was not observed. Across all types of MR, MRMVAV quantification demonstrated the highest reproducibility and consistency.

Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in Radiology and European Respiratory Journal. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society. Online supplemental material is available for this article.

Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: a) Is noninvasive imaging capable of identifying PH? b) What is the role of imaging in establishing the cause of PH? c) How does imaging determine the severity and complications of PH? d) How should imaging be used to assess chronic thromboembolic PH before treatment? e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH.

Mitral regurgitation quantification by cardiac magnetic resonance imaging (MRI) remains reproducible between software solutions.

Background: The reproducibility of mitral regurgitation (MR) quantification by cardiovascular magnetic resonance (CMR) imaging using different software solutions remains unclear. This research aimed to investigate the reproducibility of MR quantification between two software solutions: MASS (version 2019 EXP, LUMC, Netherlands) and CAAS (version 5.2, Pie Medical Imaging). Methods: CMR data of 35 patients with MR (12 primary MR, 13 mitral valve repair/replacement, and ten secondary MR) was used. Four methods of MR volume quantification were studied, including two 4D-flow CMR methods (MR MVAV and MR Jet) and two non-4D-flow techniques (MR Standard and MR LVRV). We conducted within-software and inter-software correlation and agreement analyses. Results: All methods demonstrated significant correlation between the two software solutions: MR Standard (r=0.92, p<0.001), MR LVRV (r=0.95, p<0.001), MR Jet (r=0.86, p<0.001), and MR MVAV (r=0.91, p<0.001). Between CAAS and MASS, MR Jet and MR MVAV, compared to each of the four methods, were the only methods not to be associated with significant bias. Conclusions: We conclude that 4D-flow CMR methods demonstrate equivalent reproducibility to non-4D-flow methods but greater levels of agreement between software solutions.

Cardiac-MRI Predicts Clinical Worsening and Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

OBJECTIVES: This meta-analysis evaluates assessment of pulmonary arterial hypertension (PAH), with a focus on clinical worsening and mortality. BACKGROUND: Cardiac magnetic resonance (CMR) has prognostic value in the assessment of patients with PAH. However, there are limited data on the prediction of clinical worsening, an important composite endpoint used in PAH therapy trials. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science databases were searched in May 2020. All CMR studies assessing clinical worsening and the prognosis of patients with PAH were included. Pooled hazard ratios of univariate regression analyses for CMR measurements, for prediction of clinical worsening and mortality, were calculated. RESULTS: Twenty-two studies with 1,938 participants were included in the meta-analysis. There were 18 clinical worsening events and 8 deaths per 100 patient-years. The pooled hazard ratios show that every 1% decrease in right ventricular (RV) ejection fraction is associated with a 4.9% increase in the risk of clinical worsening over 22 months of follow-up and a 2.1% increase in the risk of death over 54 months. For every 1 ml/m2 increase in RV end-systolic volume index or RV end-diastolic volume index, the risk of clinical worsening increases by 1.3% and 1%, respectively, and the risk of mortality increases by 0.9% and 0.6%. Every 1 ml/m2 decrease in left ventricular stroke volume index or left ventricular end-diastolic volume index increased the risk of death by 2.5% and 1.8%. Left ventricular parameters were not associated with clinical worsening. CONCLUSIONS: This review confirms CMR as a powerful prognostic marker in PAH in a large cohort of patients. In addition to confirming previous observations that RV function and RV and left ventricular volumes predict mortality, RV function and volumes also predict clinical worsening. This study provides a strong rationale for considering CMR as a clinically relevant endpoint for trials of PAH therapies.

Meta-analysis of echocardiographic quantification of left ventricular filling pressure.

AIMS: The clinical reliability of echocardiographic surrogate markers of left ventricular filling pressures (LVFPs) across different cardiovascular pathologies remains unanswered. The main objective was to evaluate the evidence of how effectively different echocardiographic indices estimate true LVFP. METHODS AND RESULTS: Design: this is a systematic review and meta-analysis. DATA SOURCE: Scopus, PubMed and Embase. Eligibility criteria for selecting studies were those that used echocardiography to predict or estimate pulmonary capillary wedge pressure or left ventricular end-diastolic pressures. Twenty-seven studies met criteria. Only eight studies (30%) reported both correlation coefficient and bias between non-invasive and invasively measured LVFPs. The majority of studies (74%) recorded invasive pulmonary capillary wedge pressure as a surrogate for left ventricular end-diastolic pressures. The pooled correlation coefficient overall was r = 0.69 [95% confidence interval (CI) 0.63-0.75, P < 0.01]. Evaluation by cohort demonstrated varying association: heart failure with preserved ejection fraction (11 studies, n = 575, r = 0.59, 95% CI 0.53-0.64) and heart failure with reduced ejection fraction (8 studies, n = 381, r = 0.67, 95% CI 0.61-0.72). CONCLUSIONS: Echocardiographic indices show moderate pooled association to invasively measured LVFP; however, this varies widely with disease state. In heart failure with preserved ejection fraction, no single echocardiography-based metric offers a reliable estimate. In heart failure with reduced ejection fraction, mitral inflow-derived indices (E/e', E/A, E/Vp, and EDcT) have reasonable clinical applicability. While an integrated approach of several echocardiographic metrics provides the most promise for estimating LVFP reliably, such strategies need further validation in larger, patient-specific studies.