Quantification of MRI-derived myocardial motion in specified cardiac disorders

Several cardiac diseases affect myocardial function, with local myocardial deformation receiving much attention over the past few years. This work aimed to examine whether globally and locally analyzed quantitative cardiovascular magnetic resonance imaging-derived strain, rotation, and torsion of the heart would bring additional value and deeper understanding to myocardial mechanics in specified cardiovascular disorders. Patients with rheumatoid arthritis, tetralogy of Fallot, hereditary gelsolin amyloidosis, and hypertrophic cardiomyopathy, together with healthy controls, were investigated. A non-rigid registration-based software solution for myocardial tagging and feature tracking analysis was used for the quantification of left ventricular and right ventricular global and regional strain in different directions. Quantitative motion analysis showed that early treatment of rheumatoid arthritis was useful in retaining the diastolic function of the left ventricle. In adolescents with tetralogy of Fallot, right ventricular circumferential strain was increased relative to healthy controls. Tetralogy of Fallot subjects with increased pulmonary regurgitation had higher right ventricular longitudinal strain than subjects with less pulmonary regurgitation; this has been considered a compensation mechanism. Hereditary gelsolin amyloidosis showed local myocardial changes focused on the basal plane of the left ventricle and differing from the more common light-chain cardiac amyloidosis. The non-rigid registration-based technique was compared with the harmonic phase-based method with Gabor filtering in the analysis of myocardial tagging-derived rotation and torsion in subjects with hypertrophic cardiomyopathy. The absolute values obtained with the two software methods were significantly different, however, neither software showed significant differences in patients with hypertrophic cardiomyopathy relative to healthy controls. Motion parameters of both ventricles were associated with other quantitative cardiac magnetic resonance imaging parameters, such as volumetric measurements and T1 relaxation times, in the studies of this thesis. Tagging and feature tracking-derived motion parameters showed significant findings in local myocardial motion in rheumatoid arthritis, tetralogy of Fallot,and hereditary gelsolin amyloidosis. Software-based reference values are required when comparing motion parameters between study subjects. Currently, no standardization for measuring different deformation parameters, such as strain, rotation, or torsion exists, and several software solutions are available for analyzing these parameters. Variability between different software solutions and individual observers should be recognized.Useat sydänsairaudet vaikuttavat sydänlihaksen paikalliseen liikkeeseen, jonka vuoksi sydänlihaksen liikkeen tutkiminen on herättänyt paljon mielenkiintoa muutaman viime vuoden aikana. Tämän työn tavoitteena oli tutkia magneettikuvauksessa määritettyjä sydänlihaksen globaaleja ja paikallisia kvantitatiivisia liikeparametrejä eri sydänsairauksissa. Väitöskirjan osatöissä tutkittiin nivelreumapotilaita, Fallotin tetralogia -potilaita, Meretojantautipotilaita ja hypertrofisen kardiomyopatian omaavia potilaita, yhdessä terveiden verrokkien kanssa. Elastisen kuvarekisteröinnin omaavaa ohelmistoratkaisua käytettiin sydänlihaksen kvantitatiivisen venymän mittaamiseen eri suunnissa sydämen vasenta ja oikeaa kammiota. Kvantitatiivinen liikeanalyysi osoitti, että varhaisen nivelreuman lääkehoito kannattaa, jotta sydämen vasemman kammion diastolinen funktio saadaan ylläpidettyä. Teini-ikäisillä Fallotin tetralogia -potilailla oikean kammion kehän suuntainen venymä oli selvästi voimakkaampaa kuin terveillä verrokeilla. Lisäksi Fallotin tetralogia -potilailla, joilla oli suuri pulmonaaliläpän vuoto, oli voimakkaampi oikean kammion pitkittäissuuntainen venymä, kuin potilailla, joilla vuoto oli pienempää; tämän ajateltiin olevan sydänlihaksen kompensaatiomekanismi. Meretojantautipotilailla havaittiin paikallisia sydänlihaksen liikkeen ja kudoskoostumuksen muutoksia erityisesti sydämen vasemman kammion basaalitasossa. Elastisen kuvarekisteröinnin menetelmää verrattiin harmoniseen Gabor -suodatettuun menetelmään sydänlihaksen vasemman kammion kiertymän ja väännön analysoinnissa. Näillä kahdella menetelmällä määritetyt absoluuttiset kiertymän ja väännön arvot erosivat merkittävästi toisistaan, mutta kummallakaan menetelmällä määritetyt kiertymän ja väännön arvot eivät eronneet merkittävästi hypertrofisen kardiomyopatian omaavien potilaiden ja terveiden verrokkien välillä. Sydämen vasemman ja oikean kammion liikeparametrejä verrattiin muihin kvantitatiivisiin sydämen magneettikuvauksen parametreihin, kuten kammioiden volumetrisiin mittauksiin ja sydänlihaksen T1 relaksaatioaikoihin, väitöskirjan eri osatöissä. Sydämen magneettikuvauksessa määritetyt kvantitatiivisen liikeanalyysin eri parametrit osoittivat merkittäviä löydöksiä sydänlihaksen toiminnassa nivelreumassa, Fallotin tetralogiassa ja Meretojantaudissa. Ohjelmistokohtaiset referenssiarvot ovat tarpeen, kun absoluuttisia liikeparametriarvoja vertaillaan eri yksilöiden välillä. Tällä hetkellä ei ole olemassa standardeja eri liikekomponenttien mittaamiselle ja eri ohjelmistoratkaisuja on useita erilaisia. Vaihteluväli erilaisia ohjelmistoratkaisuja käytettäessä, ja eri tarkkailijoiden välinen vaihtelu, on syytä tiedostaa

Investigating the Cardiovascular Effects of 12-months Home Based Nocturnal Haemodialysis versus. Conventional Haemodialysis Treatment: a Non-randomised Controlled Pilot Study

Living with CKD dramatically impacts an individual’s quality of life, often mandating frequent life-saving treatment in the form of haemodialysis; with its significant negative impact on cardiovascular morbidity and mortality. The cost to the individual and the NHS is substantial, with the UK ESRD population increasing by 8% year on year. The overall aim of this research was to examine the effect of nocturnal haemodialysis; an extended-hours therapy on plasma markers of oxidative stress and inflammation and compare cardiovascular outcomes with those attributed to conventional haemodialysis. The primary aim was to compare the effect of nocturnal haemodialysis on myocardial strain, as assessed by LV GLS using STE and cardiac biomarkers. The principal secondary aim was to assess the effect of nocturnal dialysis on the rate of increase of coronary calcification as a marker of coronary disease burden as assessed by CACS. In line with previous research, notably the landmark Alberta trial, FHN and FHNN trials, this thesis demonstrated an improvement in blood pressure control, serum phosphate and reduction in polypharmacy. The nocturnal group saw an improvement in LV GLS (p=0.04967) from a more significantly impaired baseline, a non-significant reduction in LVMi and no significant increase in CACS (6%). Contrasted with the conventional group where a 71.2% increase in CACS was observed (p=0.043). With regards to changes in systemic inflammation, a reduction in inflammatory marker IL-6 (p=0.04) was seen in the nocturnal group. Higher serum hepcidin levels were observed in CAC progressors than those with regression of CAC (p=0.045), where significant correlation of baseline hepcidin with relative CACS (p=0.037, r=0.9) was observed. This thesis provides new and detailed information on the assessment of cardiovascular disease in dialysis using LV GLS and CACS. Extended hours treatment with nocturnal haemodialysis significantly decreased progression of CAC compared with conventional haemodialysis. Progression appeared to be more dependent on levels of inflammation than deranged bone mineralisation with hepcidin the best predictor of an improvement in GLS and CAC progression. This information will add to the evidence-base and further enable clinicians to make person-centred therapy decisions for their ESRD patients

Myocardial fibrosis in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterised by myocardial hypertrophy, fibrosis and abnormal vascular pathology and is usually caused by mutations in sarcomeric protein genes. Histological studies and in vivo imaging with cardiac magnetic resonance imaging (CMRI) have shown that myocardial fibrosis is an important entity that contributes to disease progression. However, little is known about the regulation of genes involved in collagen synthesis and metabolism, the pathways that contribute to the development of myocardial fibrosis and whether this is an early pathological process which ultimately leads to the development of the overt phenotype in genetic mutation carriers. Furthermore, the contribution of fibrosis on myocardial function has been poorly defined. In this thesis, I identified that myocardial genetic expression of collagen is upregulated in patients with HCM and this is paralleled by elevated levels of procollagen in plasma. The genetic expression of transforming growth factor beta (TGF-β) and its downstream mediator connective tissue growth factor was also enhanced in HCM and correlated with collagen I and III RNA levels, suggesting a central role of TGF-β in mediating fibrosis. Plasma markers of collagen synthesis and metabolism were also increased in sarcomeric mutation carriers without hypertrophy, suggesting that fibrosis may be an early process that contributes to the development of the overt phenotype. Plasma levels of procollagen I were higher in patients with non-sustained ventricular tachycardia and focal fibrosis identified by CMRI was associated with impaired systolic deformation. Diffuse fibrosis beyond that seen in healthy controls also correlated with a reduction in systolic function. Together, the findings of this thesis support the hypothesis that myocardial fibrosis is an active process in HCM that precedes clinical phenotype. Myocardial fibrosis is at least in part mediated by the TGF- β pathway and associated with impaired systolic performance and may contribute to arrhythmic risk in HCM

Automated Analysis of 3D Stress Echocardiography

__Abstract__ The human circulatory system consists of the heart, blood, arteries, veins and capillaries. The heart is the muscular organ which pumps the blood through the human body (Fig. 1.1,1.2). Deoxygenated blood flows through the right atrium into the right ventricle, which pumps the blood into the pulmonary arteries. The blood is carried to the lungs, where it passes through a capillary network that enables the release of carbon dioxide and the uptake of oxygen. Oxygenated blood then returns to the heart via the pulmonary veins and flows from the left atrium into the left ventricle. The left ventricle then pumps the blood through the aorta, the major artery which supplies blood to the rest of the body [Drake et a!., 2005; Guyton and Halt 1996]. Therefore, it is vital that the cardiovascular system remains healthy. Disease of the cardiovascular system, if untreated, ultimately leads to the failure of other organs and death