Magnetic Resonance-Augmented Cardiopulmonary Exercise Testing Comprehensively Assessing Exercise Intolerance in Children with Cardiovascular Disease

BACKGROUND: Conventional cardiopulmonary exercise testing can objectively measure exercise intolerance but cannot provide comprehensive evaluation of physiology. This requires additional assessment of cardiac output and arteriovenous oxygen content difference. We developed magnetic resonance (MR)–augmented cardiopulmonary exercise testing to achieve this goal and assessed children with right heart disease. METHODS AND RESULTS: Healthy controls (n=10) and children with pulmonary arterial hypertension (PAH; n=10) and repaired tetralogy of Fallot (n=10) underwent MR-augmented cardiopulmonary exercise testing. All exercises were performed on an MR-compatible ergometer, and oxygen uptake was continuously acquired using a modified metabolic cart. Simultaneous cardiac output was measured using a real-time MR flow sequence and combined with oxygen uptake to calculate arteriovenous oxygen content difference. Peak oxygen uptake was significantly lower in the PAH group (12.6±1.31 mL/kg per minute; P=0.01) and trended toward lower in the tetralogy of Fallot group (13.5±1.29 mL/kg per minute; P=0.06) compared with controls (16.7±1.37 mL/kg per minute). Although tetralogy of Fallot patients had the largest increase in cardiac output, they had lower resting (3±1.2 L/min per m2) and peak (5.3±1.2 L/min per m2) values compared with controls (resting 4.3±1.2 L/min per m2 and peak 6.6±1.2 L/min per m2) and PAH patients (resting 4.5±1.1 L/min per m2 and peak 5.9±1.1 L/min per m2). Both the PAH and tetralogy of Fallot patients had blunted exercise–induced increases in arteriovenous oxygen content difference. However, only the PAH patients had significantly reduced peak values (6.9±1.3 mlO2/100 mL) compared with controls (8.4±1.4 mlO2/100 mL; P=0.005). CONCLUSIONS: MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference

Real time magnetic resonance assessment of septal curvature accurately tracks acute hemodynamic changes in pediatric pulmonary hypertension

International audienceBACKGROUND:This study assesses the relationship between septal curvature and mean pulmonary artery pressure and indexed pulmonary vascular resistance in children with pulmonary hypertension. We hypothesized that septal curvature could be used to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics.METHODS AND RESULTS:Fifty patients with a median age of 6.7 years (range, 0.45-16.5 years) underwent combined cardiac catheterization and cardiovascular magnetic resonance. The majority had idiopathic pulmonary arterial hypertension (n=30); the remaining patients had pulmonary hypertension associated with repaired congenital heart disease (n=17) or lung disease (n=3). Mean pulmonary artery pressure and pulmonary vascular resistance were acquired at baseline and during vasodilation. Septal curvature was measured using real-time cardiovascular magnetic resonance. There was a strong correlation between mean pulmonary artery pressure and SCmin at baseline and during vasodilator testing (r=-0.81 and -0.85, respectively; P<0.01). A strong linear relationship also existed between pulmonary vascular resistance and minimum septal curvature indexed to cardiac output both at baseline and during vasodilator testing (r=-0.88 and -0.87, respectively; P<0.01). Change in septal curvature metrics moderately correlated with absolute change in mean pulmonary artery pressure and pulmonary vascular resistance, respectively (r=0.58 and -0.74; P<0.01). Septal curvature metrics were able to identify vasoresponders with a sensitivity of 83% (95% confidence interval, 0.36-0.99) and a specificity of 91% (95% confidence interval, 0.77-0.97), using the Sitbon criteria. Idiopathic pulmonary arterial hypertension subgroup analysis revealed 3 responders with ΔSCmin values of 0.523, 0.551, and 0.568. If the middle value of 0.551 is taken as a cutoff, the approximate sensitivity would be 67% and the specificity would be 93%.CONCLUSIONS:Septal curvature metrics are able to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics during vasodilator testing. This suggests that septal curvature could be used for continuing assessment of load in pulmonary hypertension

Filamin A (FLNA) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification

AIM: Interstitial lung disease (ILD) in infants represents a rare and heterogenous group of disorders, distinct from those occurring in adults. In recent years a new entity within this category is being recognized, namely filamin A (FLNA) mutation related lung disease. Our aims are to describe the clinical and radiological course of patients with this disease entity to aid clinicians in the prognostic counseling and management of similar patients they may encounter. METHOD: A retrospective case note review was conducted of all patients treated at our institution (a specialist tertiary referral childrens’ center) for genetically confirmed FLNA mutation related lung disease. The clinical presentation, evolution, management and radiological features were recorded and a medical literature review of Medline indexed articles was conducted. RESULTS: We present a case series of four patients with interstitial lung disease and genetically confirmed abnormalities within the FLNA gene. Their imaging findings all reveal a pattern of predominantly upper lobe overinflation, coarse pulmonary lobular septal thickening and diffuse patchy atelectasis. The clinical outcomes of our patients have been variable ranging from infant death, lobar resection and need for supplemental oxygen and bronchodilators. CONCLUSION: The progressive nature of the pulmonary aspect of this disorder and need for early aggressive supportive treatment make identification crucial to patient management and prognostic counseling

Impact of intracoronary imaging-guided percutaneous coronary intervention on procedural outcomes among complex patient groups

Background Intracoronary imaging (ICI) has been previously shown to improve survival and clinical outcomes after percutaneous coronary intervention (PCI). However, whether this prognostic benefit is sustained across different indications/patient groups remains unclear. Methods All PCI procedures performed in England and Wales between 1st April 2014 and 31st March 2020 were retrospectively analysed. The association between ICI use and in-hospital MACCE (major adverse cardiovascular and cerebrovascular outcomes; composite of all-cause mortality, stroke and reinfarction) and mortality was examined using multivariable logistic regression analysis for each imaging-recommended indication (stent thrombosis (ST), in-stent restenosis, stent length&amp;gt;60mm, acute coronary syndrome (ACS) indications, chronic total occlusion, left main stem (LMS) intervention, renal failure and bioresorbable vascular scaffolds (BVS)). Results Of 555,398 PCI procedures, 10.8% (n=59,752) were performed under ICI guidance. ICI use doubled between 2014 (7.8%) and 2020 (17.5%). ICI use was highest for BVS (44.7%) and LMS PCI (41.2%) cases and lowest in ACS (9%). Overall, the odds ratios (OR) of in-hospital MACCE and mortality were only reduced with ICI-guided PCI in cases with an imaging-recommended indication (OR 0.75 95% confidence interval (CI) 0.69-0.81 and OR 0.69 95%CI 0.63-0.76, respectively). Only specific imaging-recommended indications were associated with reduced MACCE and mortality, including LMS PCI (OR 0.45 95%CI 0.39-0.52 and 0.41 95%CI 0.35-0.48, respectively), ACS (OR 0.76 95%CI 0.70-0.82 and 0.70 95%CI 0.63-0.77), stent length&amp;gt;60mm (OR 0.75 95%CI 0.59-0.94 and 0.72 95%CI 0.54-0.95). ST was only associated with lower mortality (OR: 0.69 95%CI 0.52-0.91) while renal failure was associated with reduced MACCE (OR 0.77 95%CI 0.60-0.99) but not mortality. (Figure 1) Conclusion The utilisation of ICI has more than doubled over a seven-year period at a national level but remains low, with less than 1-in-5 procedures performed under ICI guidance. In-hospital survival was better with ICI-guided than angiography-guided PCI, albeit only for specific indications.Figure

Impact of Intracoronary Imaging-Guided Percutaneous Coronary Intervention on Procedural Outcomes Among Complex Patient Groups.

Background Intracoronary imaging (ICI) has been shown to improve survival after percutaneous coronary intervention (PCI). Whether this prognostic benefit is sustained across different indications remains unclear. Methods and Results All PCI procedures performed in England and Wales between April, 2014 and March 31, 2020, were retrospectively analyzed. The association between ICI use and in-hospital major acute cardiovascular and cerebrovascular events; composite of all-cause mortality, stroke, and reinfarction and mortality was examined using multivariable logistic regression analysis for different imaging-recommended indications as set by European Association for Percutaneous Cardiovascular Interventions consensus. Of 555 398 PCI procedures, 10.8% (n=59 752) were ICI-guided. ICI use doubled between 2014 (7.8%) and 2020 (17.5%) and was highest in left main PCI (41.2%) and lowest in acute coronary syndrome (9%). Only specific European Association for Percutaneous Cardiovascular Interventions imaging-recommended indications were associated with reduced major acute cardiovascular and cerebrovascular events and mortality, including left main PCI (odds ratio [OR], 0.45 [95% CI, 0.39-0.52] and 0.41 [95% CI, 0.35-0.48], respectively), acute coronary syndrome (OR, 0.76 [95% CI, 0.70-0.82] and 0.70 [95% CI, 0.63-0.77]), and stent length >60 mm (OR, 0.75 [95% CI, 0.59-0.94] and 0.72 [95% CI, 0.54-0.95]). Stent thrombosis and renal failure were associated with lower mortality (OR, 0.69 [95% CI, 0.52-0.91]) and major acute cardiovascular and cerebrovascular events (OR, 0.77 [95% CI, 0.60-0.99]), respectively. Conclusions ICI use has more than doubled over a 7-year period at a national level but remains low, with <1 in 5 procedures performed under ICI guidance. In-hospital survival was better with ICI-guided than angiography-guided PCI, albeit only for specific indications

Prostanoid EP₂ Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells

Prostacyclins are extensively used to treat pulmonary arterial hypertension (PAH), a life-threatening disease involving the progressive thickening of small pulmonary arteries. Although these agents are considered to act therapeutically via the prostanoid IP receptor, treprostinil is the only prostacyclin mimetic that potently binds to the prostanoid EP₂ receptor, the role of which is unknown in PAH. We hypothesised that EP₂ receptors contribute to the anti-proliferative effects of treprostinil in human pulmonary arterial smooth muscle cells (PASMCs), contrasting with selexipag, a non-prostanoid selective IP agonist. Human PASMCs from PAH patients were used to assess prostanoid receptor expression, cell proliferation, and cyclic adenosine monophosphate (cAMP) levels following the addition of agonists, antagonists or EP₂ receptor small interfering RNAs (siRNAs). Immunohistochemical staining was performed in lung sections from control and PAH patients. We demonstrate using selective IP (RO1138452) and EP₂ (PF-04418948) antagonists that the anti-proliferative actions of treprostinil depend largely on EP₂ receptors rather than IP receptors, unlike MRE-269 (selexipag-active metabolite). Likewise, EP₂ receptor knockdown selectively reduced the functional responses to treprostinil but not MRE-269. Furthermore, EP₂ receptor levels were enhanced in human PASMCs and in lung sections from PAH patients compared to controls. Thus, EP₂ receptors represent a novel therapeutic target for treprostinil, highlighting key pharmacological differences between prostacyclin mimetics used in PAH

Cardiac catheterization in children with pulmonary hypertensive vascular disease:Consensus statement from the Pulmonary Vascular Research Institute, Pediatric and Congenital Heart Disease Task Forces

Cardiac catheterization is important in the diagnosis and risk stratification of pulmonary hypertensive vascular disease (PHVD) in children. Acute vasoreactivity testing provides key information about management, prognosis, therapeutic strategies, and efficacy. Data obtained at cardiac catheterization continue to play an important role in determining the surgical options for children with congenital heart disease and clinical evidence of increased pulmonary vascular resistance. The Pediatric and Congenital Heart Disease Task Forces of the Pulmonary Vascular Research Institute met to develop a consensus statement regarding indications for, conduct of, acute vasoreactivity testing with, and pitfalls and risks of cardiac catheterization in children with PHVD. This document contains the essentials of those discussions to provide a rationale for the hemodynamic assessment by cardiac catheterization of children with PHVD.</p