MR-Conditional Cardiovascular Implantable Electronic Devices in Patients With Congenital Heart Disease: A Real Gain?
Grace HT Kwok1*, Bram Ruijsink2, Srinivas Narayan1, Kuberan Pushparajah1, Henry Chubb1, Yaso Emmanuel1, Harith Alam1, Eric Rosenthal1 and Alessandra Frigiola1,2
1Guy’s and St. Thomas’ NHS Foundation Trust, Westminster Bridge Road, Lambeth, London, SE1 7EH
2King’s College London, Guy’s Campus, Great Maze Road, London, SE1 1UL
*Address for Correspondence: Grace HT Kwok, Guy’s and St. Thomas’ NHS Foundation Trust, Westminster Bridge Road, Lambeth, London, SE1 7EH, E-mail: Grace.email@example.com
Submitted: 26 February 2021; Approved: 08 March 2021; Published: 11 March 2021
Citation this article: Kwok GHT, Ruijsink B, Narayan S, Pushparajah K, Chubb H, Emmanuel Y, Alam H, Rosenthal E, Frigiola A. MR-Conditional Cardiovascular Implantable Electronic Devices in Patients With Congenital Heart Disease: A Real Gain? Int J Cardiovasc Dis Diagn. 2021 Mar 11;6(1): 017-024.
Copyright: © 2021 Kwok GHT, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Keywords: Congenital heart disease; Cardiovascular magnetic resonance; Cardiovascular implantable electronic devices; Fontan; Artefacts
Background: MR-conditional Cardiovascular Implantable Electronic Devices (CIED) enables patients with CIED to have MRI scans. While the safety profile of MR-conditional CIEDs is encouraging, artefacts from CIED are unavoidable. This study aims to provide a qualitative evaluation on the extent of CIED artefacts for patients with Congenital Heart Disease (CHD) undergoing Cardiac MRI (CMR).
Methods: This is a retrospective study of all patients with CHD and MR-conditional CIEDs who underwent CMR between 10/10/2011 and 04/09/2018 at our level one surgical centre for CHD. Patients were included in the study if they have a structural CHD, had a CIED inserted and had a CMR scan with the CIED in situ. Images were acquired on a 1.5T MRI Scanner. Low Specific Absorption Rate (SAR) mode was activated on the MRI scanner to keep SAR levels below 2 Watts/kg. Retrospective gated steady-state free precession cine MRI of the heart were acquired in vertical long-axis, 4-chamber view and the short-axis view covering the entirety of both ventricles (9 to 12 slices). The extent of artefacts on diagnosis were graded from 1 to 4 in cardiac anatomy, flows, volumes and overall diagnostic value by two cardiologists.
Results: 17 patients received a CIED at a median age of 18 years (range 3-56 years) and underwent a CMR scan within the studied timeframe. 59% of the scans were of acceptable to good diagnostic quality (grades 1/2, n = 10). Assessment of cardiac volumes was most affected (53% of scans graded 1/2), followed by cardiac anatomy (59% grades 1/2). Flow analysis was most robust (81% grades 1/2). Contralateral PM sites appeared to be associated with overall better quality.
Conclusion: Over half of the patients had an acceptable quality scan. Anatomy and volumes were significantly affected by CIED artefacts, which may have implications for accurate assessment.
AOO: Asynchronous Atrial Pacing Mode; B-SSFP: Balanced Steady-State Free Precession; C/Contra: CIED Implanted on the Contralateral Side of the Heart; Cctga: Congenitally Corrected Transposition of the Great Arteries (Cctga); CHD: Congenital Heart Disease; CIED: MR-Conditional Cardiovascular Implantable Electronic Devices; CMR: Cardiovascular Magnetic Resonance Imaging; DILV: Double Inlet Left Ventricle; EF: Ejection Fraction; FFE: Fast Field Echo Sequence; HLHS: Hypoplastic Left Heart Syndrome; I/Ipsi: CIED Implanted on the Ipsilateral Side of the Heart; ICD: Implantatable Cardioverter Defibrillator; IVC: Inferior Vena Cava; LPA: Left Pulmonary Artery; MRI: Magnetic Resonance Imaging; PA: Pulmonary Artery; PM: Pacemaker (Used Interchangably With CIED in this Paper); RPA: Right Pulmonary Artery; RVOT: Right Ventricular Outflow Tract; SAR: Low Specific Absorption Rate; SV: Stroke Volume; SVC: Superior Vena Cava; TE: Time to Echo (Time Between Delivery Of The Radiofrequency Pulse To Receipt Of The Echo Signal); TGA: Transposition of the Great Arteries; Tof: Tetralogy Of Fallot; TR: Receptive Time (Time Between Successive Pulse Sequences Applied to The Same Slice); VA: Ventriculo-Arterial; VSD: Ventricular Septic Defect
Plants have always been an important source of drug leads and novel drugs for the treatment of many different conditions and diseases. The hemp plant, Cannabis sativa L., was classified in 1975 and is commonly used for its euphoric mood altering effects . Cannabis sativa L. contains phytocannabinoids, which are bioactive compounds extracted from the plant that are capable of interacting with cannabinoid receptors found on many different cell types . Phytocannabinoids have recently gained a lot of attention for their potential medical properties and uses in western medicine . To date, over 100 phytocannabinoids have been isolated from the Cannabis sativa L. plant . The most abundant, well-known, and well-studied phytocannabinoid is tetrahydrocannabinol (THC) . Although THC has been shown to help with conditions including multiple sclerosis , chronic pain  and chemotherapy-induced nausea , the drawback is its psychoactive effect. CBD is another abundant plant-derived phytocannabinoid isolated from Cannabis sativa L . Structurally, CBD is very similar to THC, however it is devoid of the psychoactive symptoms making it a more desirable pharmaceutical compound. In 2018, the Food and Drug Administration approved Epidiolex, an oral CBD solution, as an anti-epileptic drug . Many other medicinal properties of CBD are currently being examined. A major area of CBD research is focussed upon investigating the anti-inflammatory properties of CBD and its potential medicinal contribution to cardiovascular diseases [11,13]. CBD has also been shown to induce vasorelaxation in normotensive rat models  and human mesenteric arteries .
CBD Receptors in the Endocannabinoid System (ECS)
There are two major G-protein coupled receptors for cannabinoids, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) . CB1 is highly expressed in the central nervous system and to some extent in peripheral tissues. CB2 is located in many peripheral tissues, including the cardiovascular system, and is also highly expressed in immune cells . The endocannabinoid system (ECS) is a homeostatic regulator of many physiological systems in the body, including energy balance, appetite, pain-sensation, blood pressure, mood, embryogenesis, nausea and vomiting control, memory, learning and immune response . CBD’s association with cannabinoid receptors is not well defined, however, it is believed that CBD is a partial antagonist for CB1 and partial agonist for CB2 . CB2 was initially thought to be an optimal target for inhibiting atherosclerosis progression. However, genetic knockout of CB2 did not affect the size of atherosclerotic plaques in high cholesterol diet fed low-density lipoprotein receptor knockout mouse model .
CBD can also interact with non- cannabinoid receptors including the peroxisome proliferator-activated receptors (PPAR) [19,20]. PPARs are nuclear receptors that control gene transcription by forming heterodimers with the retinoid X receptor and binding to the peroxisome proliferator hormone response element (PPRE) of target genes . PPARs are present in 3 isoforms, PPARα/β/γ, and are widely expressed in the body . They have a large ligand binding domain and interact with various compounds . Recent evidence, from binding studies, reporter gene assays, the use of selective antagonists, siRNA knockdown studies, and knockout animals suggest that therapeutic effects of CBD are mediated through CBD-PPARγ binding . Myeloid-specific genetic PPARγ-deficient mice have increased aortic atherosclerosis, suggesting that PPARγ is an important receptor for slowing the progression of atherosclerosis . PPARy has been the focus for many anti-diabetic drugs and is known to regulate adipocyte differentiation, fatty acid storage and glucose metabolism . Additionally, PPARy activators have been shown to inhibit the expression of ICAM and VCAM and therefore may contribute to reduced monocyte attachment to endothelial cells, resulting in attenuated plaque development [24,25]. Other agonists of PPARγ, including the thiazolidinediones (TZD), have also shown promise in pre-clinical studies as anti-atherogenic drugs .
CBD and Atherosclerosis
CBD has been approved for recreational and medical use in Canada and several States, and is currently being tested in the treatment of a plethora of diseases. One major advantage of CDB is that it appears to lack any major detrimental side effects. Despite the limited research on CBD and its effects on the vascular system and atherosclerosis, CBD is currently being marketed as a natural vasorelaxant compound with potential anti-atherogenic effects. A number of studies have discovered an anti-inflammatory and cardio-protective function of CBD when tested in animal models of diabetes [26,27], myocardial infarction  and stress . However, the effects of CBD administration on atherosclerosis have not yet been definitively assessed. More research is required to explore the therapeutic potential of CDB in the treatment of atherosclerotic cardiovascular disease.
This work was supported by an operational grant from the Canadian Institutes for Health Research (PJT-166092). GHW is supported by an HSFC Ontario Mid-Career Investigator Award.
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