Cellular therapy for cardiovascular disease Part 2 - Delivery of cells and clinical experience

Peter J Psaltis, Stan Gronthos, Stephen G Worthley and Andrew C.W. Zannettin

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial

Aims: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN™ multi-electrode system. Methods and results: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by −28/10, −27/10 and −26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Conclusion: Renal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension.Stephen G. Worthley, Costas P. Tsioufis, Matthew I. Worthley, Ajay Sinhal, Derek P. Chew, Ian T. Meredith, Yuvi Malaiapan, and Vasilios Papademetrio

Flow in left atrium using MR fluid motion estimation

Copyright 2007 Society of Photo-Optical Instrumentation Engineers. This paper was published in Complex Systems II, edited by Derek Abbott, Tomaso Aste, Murray Batchelor, Robert Dewar, Tiziana Di Matteo, Tony Guttmann, Proc. of SPIE Vol. 6802, 68021H and is made available as an electronic reprint with permission of SPIE. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.A recent development based on optical flow applied onto Fast Imaging in Steady State Free Precession (TrueFISP) magnetic resonance imaging is able to deliver good estimation of the flow profile in the human heart chamber. The examination of cardiac flow based on tracking of MR signals emitted by moving blood is able to give medical doctors insight into the flow patterns within the human heart using standard MRI procedure without specifically subjecting the patient to longer scan times using more dedicated scan protocols such as phase contrast MRI. Although MR fluid motion estimation has its limitations in terms of accurate flow mapping, the use of a comparatively quick scan procedure and computational post-processing gives satisfactory flow quantification and can assist in management of cardiac patients. In this study, we present flow in the left atria of five human subjects using MR fluid motion tracking. The measured flow shows that vortices exist within the atrium of heart. Although the scan is two-dimensional, we have produced multiple slices of flow maps in a spatial direction to show that the vortex exist in a three-dimensional space.Kelvin K. L. Wong, Richard M. Kelso, Stephen M. Worthley, Prash Sanders, Jagannath Mazumdar, Derek Abbot

Enter evaluation of mitral inflow velocity profile: optimal through plane location for mitral inflow assessment with cardiac magnetic resonance

Diastology is usually assessed using transthoracic echocardiography (TTE). Velocity‐encoded phase‐contrast imaging permits evaluation with cardiac magnetic resonance (CMR). Heterogeneous contour locations have been used to measure mitral (MV) inflow velocities and the optimal contour location is uncertain. We evaluated CMR MV inflow velocities against TTE to identify the optimal location

Assessment of atrial septal defects in adults comparing cardiovascular magnetic resonance with transoesophageal echocardiography

BackgroundMany adult patients with secundum-type atrial septal defects (ASDs) are able to have these defects fixed percutaneously. Traditionally, this has involved an assessment of ASD size, geometry and atrial septal margins by transoesophageal echocardiography (TOE) prior to percutaneous closure. This is a semi-invasive technique, and all of the information obtained could potentially be obtained by non-invasive cardiovascular magnetic resonance (CMR). We compared the assessment of ASDs in consecutive patients being considered for percutaneous ASD closure using CMR and TOE.MethodsConsecutive patients with ASDs diagnosed on transthoracic echocardiography (TTE) were invited to undergo both CMR and TOE. Assessment of atrial septal margins, maximal and minimal defect dimensions was performed with both techniques. Analyses between CMR and TOE were made using simple linear regression and Bland Altman Analyses.ResultsTotal CMR scan time was 20 minutes, and comparable to the TOE examination time. A total of 20 patients (M:F = 5:15, mean age 42.8 years +/- 15.7) were included in the analyses. There was an excellent agreement between CMR and TOE for estimation of maximum defect size (R = 0.87). The anterior inferior, anterior superior and posterior inferior margins could be assessed in all patients with CMR. The posterior superior margin could not be assessed in only one patient. Furthermore, in 1 patient in whom TOE was unable to be performed, CMR was used to successfully direct percutaneous ASD closure.ConclusionsCMR agrees with TOE assessment of ASDs in the work-up for percutaneous closure. Potentially CMR could be used instead of TOE for this purpose.Karen S.L. Teo, Patrick J. Disney, Benjamin K. Dundon, Matthew I. Worthley, Michael A. Brown, Prashanthan Sanders and Stephen G. Worthle

Motion estimation of vortical blood flow within the right atrium in a patient with atrial septal defect

Copyright © 2007 IEEEPatients with an atrial septal defect (ASD) have a left to right shunt with associated complications. Currently, various imaging modalities, including echocardiography and invasive cardiac catheterization, are utilized in the management of these patients. Cardiac magnetic resonance (CMR) imaging provides a novel and non-invasive approach for imaging patients with ASDs. A study of vortices generated within the right atrium (RA) during the diastolic phase of the cardiac cycle can provide useful information on the change in the magnitude of vorticity pre-and post-ASD closure. The motion estimation of blood applied to CMR is performed. In this study we present, a two dimensional (2D) visualization of in-vivo right atrial flow. This is constructed using flow velocities measured from the intensity shifts of turbulent blood flow regions in MRI. In particular, the flow vortices can be quantified and measured, against controls and patients with ASD, to extend medical knowledge of septal defects and their haemodynamic effects.Kelvin K.L. Wong, P. Molaee, P. Kuklik, Richard M. Kelso, S.G Worthley, P. Sanders, J. Mazumdar and D. Abbot

Noninvasive Cardiac Flow Assessment Using High Speed Magnetic Resonance Fluid Motion Tracking

Cardiovascular diseases can be diagnosed by assessing abnormal flow behavior in the heart. We introduce, for the first time, a magnetic resonance imaging-based diagnostic that produces sectional flow maps of cardiac chambers, and presents cardiac analysis based on the flow information. Using steady-state free precession magnetic resonance images of blood, we demonstrate intensity contrast between asynchronous and synchronous proton spins. Turbulent blood flow in cardiac chambers contains asynchronous blood proton spins whose concentration affects the signal intensities that are registered onto the magnetic resonance images. Application of intensity flow tracking based on their non-uniform signal concentrations provides a flow field map of the blood motion. We verify this theory in a patient with an atrial septal defect whose chamber blood flow vortices vary in speed of rotation before and after septal occlusion. Based on the measurement of cardiac flow vorticity in our implementation, we establish a relationship between atrial vorticity and septal defect. The developed system has the potential to be used as a prognostic and investigative tool for assessment of cardiac abnormalities, and can be exploited in parallel to examining myocardial defects using steady-state free precession magnetic resonance images of the heart