Emmanuel Ako

Magnetic Resonance–Augmented Cardiopulmonary Exercise TestingCLINICAL PERSPECTIVE: 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.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.

UNDERSTANDING THE CARDIOPULMONARY CIRCULATION IN SICKLE CELL DISEASE: USING AN MR AUGMENTED CARDIOPULMONARY EXERCISE TESTING TECHNIQUE

Exercise intolerance is a common feature of many diseases. The causes are difficult to determine and often multifactorial, including secondary cardiac-respiratory dysfunction, as well as skeletal muscle abnormalities. We have developed MR augmented cardiopulmonary exercise testing (CPET) that allows

Ultrafast CMR to deliver high volume screening of an at risk thalassemia population in the developing world: preliminary results from the TIC-TOC study (Thailand and UK international collaboration in thalassaemia using an optimised ultrafast CMR protocol)

Ultrafast CMR to deliver high volume screening of an at risk thalassemia population in the developing world: preliminary results from the TIC-TOC study (Thailand and UK international collaboration in thalassaemia using an optimised ultrafast CMR protocol) Amna Abdel-Gadir, Yongkasem Vorasettakarnkij, Hataichanok Ngamkasem, Sabrina Nordin, Emmanuel O Ako, Monravee Tumkosit, Pranee Sutcharitchan, Peter Kellman, Stefan K Piechnik, Juliano L Fernandes, Mark Westwood, John Porter, John Malcolm Walker, James Moon

MR-Augmented Cardiopulmonary Exercise Testing- a proof of concept in Sickle Cell Disease (SCD)

Background Exercise intolerance is a common feature of many noncardiac and non-respiratory diseases. The causes are often multifactorial and include secondary cardiac-respiratory dysfunction, as well as skeletal muscle abnormalities. Unfortunately, it is difficult to determine the exact cause using conventional cardiopulmonary exercise testing (CPET). Therefore, we have developed MR augmented CPET that allows simultaneous evaluation of cardiac output and tissue oxygen extraction in addition to conventional CPET measures. To demonstrate the utility of this technique we performed MR-CPET on patients with sickle cell disease (SCD). The aim of this study was to demonstrate that MR-CPET could be used to define the physiological factors associated with their poorly understood exercise intolerance.

CARDIOVASCULAR COMPLICATIONS IN SICKLE CELL DISEASE

Sickle cell disease (SCD) is a genetic disorder affecting the production of haemoglobin (Hb). It has life-long consequences with multi-organ involvement, including the cardiopulmonary circulation and an increased mortality. Although all SCD patients share the genetic defect, the phenotype varies.

A NOVEL NON-INVASIVE METHOD OF ASSESSING CARDIOVASCULAR FUNCTION USING MAGNETIC RESONANCE AUGMENTED CARDIOPULMONARY EXERCISE TESTING

Background: Reduced exercise capacity is a common feature of many cardiovascular diseases. Quantitative assessment of exercise capacity is usually achieved by conventional CPET measuring peak oxygen consumption (VO2). However this neglects different components of reduced exercise capacity namely reduced cardiac output (CO) and oxygen extraction (ΔcO2). This study aims to demonstrate a comprehensive approach to simultaneously measure VO2 and CO and then calculate ΔcO2.

MR augmented cardiopulmonary exercise testing - a novel method of assessing cardiovascular function

Background Reduced exercise capacity is a common feature of many cardiovascular diseases. Quantitative assessment of exercise capacity is usually achieved by measuring peak oxygen consumption (VO2). However, measuring peak VO2 alone neglects the different components of reduced exercise capacity: namely reduced cardiac output (CO) and oxygen extraction (ΔcO2). A better approach would be to simultaneously measure VO2 and CO and then calculate ΔcO2. This could be achieved using MR augmented cardio-pulmonary exercise testing (MR-CPET) The aims of this study were to demonstrate: 1) MRCPET is feasible and well tolerated, 2) peak VO2 in the MR scanner correlates with conventional peak VO2, and 3) variation in peak VO2 is related to both peak CO and peak oxygen extraction (ΔcO2) as calculated by the Fick equation.

135 Cardiovascular Complications in Sickle Cell Disease

Introduction Sickle cell disease (SCD) is a genetic disorder affecting the production of haemoglobin (Hb). It has life-long consequences with multi-organ involvement including the cardiopulmonary circulation and an increased mortality. Although all SCD patients share the same genetic defect, the phenotype varies. This suggests other factors, unrelated to the Hb mutation, play an important role particularly in later decades. This retrospective study examined patient survival attending a specialist tertiary centre in the United Kingdom based on Tricuspid Regurgitant Jet Velocity (TRJ) measured by echocardiography and associated laboratory studies. Method A retrospective analysis of TRJ and diastolic function (lateral E/E’ ratio) assessed by echocardiography in 127 intensively treated steady-state SCD patients (mean age 40 +/- 12 years) screened for cardiovascular complications. Laboratory studies were also analysed. Results The clinical characteristics of patients in this study is summarised in Table 1. 15% of patients had a TRJ between 2.6–2.99 m/s and 9% with TRJ >3.0 m/s. 11% of patients had diastolic dysfunction using lateral E/E’ ratio. Abstract 135 Table 1 Clinical characteristics of SCD patients Variable Number Summary Male gender – n (%) 127 50 (39%) Age – mean (SD) 127 40 (12) TRJ – mean (SD) 127 1.6 (1.1) Haemoglobin (g/l) – mean (SD) 127 9.0 (1.5) Reticulocyte (%) – median (IQR) 127 7 (4.41, 10.13) Ejection Fraction (%) – mean (SD) 127 63 (9) Lateral E/E’ ratio – mean (SD) 127 7.79 (3.27) Transfusion – n (%) 127 45 (35%) Hydoxycarbamide – n (%) 127 41 (32%) When compared to patients with a TRJ <2.5 m/s, the risk of death is 4 times higher in the 2.6–2.99 TRJ group and 24 times higher in the > 3.0 TRJ group. See Figure 1. Abstract 135 Figure 1 Kaplan-Meier survival curves for SCD patients arranged according to TRJ range Lateral E/E’ ratio (beta = 0.88, p = 0.015), left atrial area (beta = 0.38, p < 0.001) and microalbuminuria (beta = 0.10, p = 0.05) were independently associated with TRJ. Conclusion Mortality in SCD patients with raised TRJ remains high despite intensive therapy, such as exchange transfusion, directed at correcting Hb. Screening with echocardiography remains an important tool in identifying high-risk patients. Additional therapies directed at the premature ageing of the cardiopulmonary circulation are urgently needed.

134 MR Augmented Cardiopulmonary Exercise Testing – a Novel Way of Assessing Cardiovascular Function

Introduction Reduced exercise capacity is a common feature of many cardiovascular diseases. Quantitative assessment of exercise capacity is usually achieved by measuring peak oxygen consumption (VO2). However, measuring peak VO2 alone neglects the different components of reduced exercise capacity: namely reduced cardiac output (CO) and oxygen extraction (ΔcO2). A better approach would be to simultaneously measure VO2 and CO and then calculate ΔcO2. This could be achieved using MR augmented cardiopulmonary exercise testing (MR-CPET). The aims of this study were to demonstrate: 1) MR-CPET is feasible and well tolerated, 2) peak VO2 in the MR scanner correlates with conventional peak VO2 and 3) variation in peak VO2 is related to both peak CO and peak oxygen extraction (ΔcO2) as calculated by the Fick equation. Method 17 healthy volunteers (21–55 years) underwent MR-CPET. Exercise was performed on an MR-compatible ergometer (Lode, Groningen, The Netherlands) and VO2 was assessed using a commercial respiratory gas analyser (Ultima, MedGraphics, St. Paul, USA) with a modified sampling tube that was MR compatible. Set-up for MR-CPET is shown in Figure 1. Aortic flow was continuously measured using a previously validated UNFOLD-SENSE spiral PCMR sequence. Images were reconstructed using a graphical processing unit card and analysed using an in-house plug-in for OsiriX software. Conventional CPET was also performed within 2 weeks of MR-CPET. For both tests, participants were asked to rate i) concern ii) comfort and iii) perceived helplessness. Abstract 134 Figure 1 Set-up for MR-CPET: a) subject in exercise position on MR compatible ergometer b) subject with facemask attached to MR compatible umbilicus passing through the wave-guide Results 15 out of 17 volunteers completed exercise; exclusions were due to claustrophobia (n = 1) and inability to master exercise technique (n = 1). Reported concern and discomfort was higher with MR-CPET, although still within acceptable limits. Peak VO2, peak VCO2 and VE showed strong correlation between conventional CPET and MR-CPET: VO2 peak (r = 0.94, p < 0.001); VCO2 (r = 0.87, p < 0.001); VE (r = 0.88, p < 0.001). Resting and peak values VO2, CO, HR, SV and ΔcO2 are shown in Table 1. Multiple linear regression analysis demonstrated that both peak CO and ΔcO2 were independent predictors of peak VO2 measured during MR-CPET (beta = 0.73 and 0.38 respectively, p < 0.001) and conventional CPET (beta = 0.78 and 0.28 respectively, p < 0.001). Abstract 134 Table 1 Values at rest and Peak VO2 obtained at MR-CPET Conclusion MR-CPET is feasible, well tolerated and demonstrates physiology not apparent with conventional CPET. In this study, we have shown that MR-CPET allows assessment of the differing contributions of CO and ΔcO2 to variation in peak VO2. We believe that will be useful in understanding the origin of reduced exercise capacity in cardiac disease.