Hjertefunksjon og livskvalitet hos unge
I samarbeid med
Søknadssammendrag
Prosjekttema (på norsk)
Behandling med allogen stamcelle transplantasjon (ALLOs) er ved visse kreftformer den eneste vei til helbredelse, men har en rekke komplikasjoner. Hvert år får omtrent 30 barn og unge slik behandling i Norge. Lite er kjent om hvordan behandlingen virker på hjertefunksjonen hos barn og unge. Slik kunnskap er nødvendig for å lage gode livslange oppfølgingsrutiner. I en nasjonal studie over 150 barn og unge som har gjennomgått ALLOS ønsker vi i denne studien spesifikt å kartlegge: 1. Hjertemuskelfunksjon i høyre og venstre hovedkammer 2. Hjerteklaffefunksjon 3. Fysisk yteevne og livskvalitet 4. Optimalisere medisinsk rehabilitering og oppfølging av barn og unge etter ALLOs. Denne studien er del av et større nasjonalt prosjekt som bredt kartlegger fysisk og psykisk tilstand hos en stor gruppe barnekreftpasienter som har overlevd allogen stamcelletransplantasjon (ALLOs). I alt deltar ca 150 pasienter i studien. I denne delstudien vil vi se spesifikt på hjerte- og karfunksjon hos disse pasientene 5-15 år etter den opprinnelige ALLOs behandlingen. Hjerteundersøkelser inklusive hjerteultralyd (ekkokardiografi), MRI, ergospirometri (arbeidstester) vil bli gjennomført. Prosjektet leverer et vell av kvalitetsdata som gir gode muligheter for en grundig kartlegging av disse pasientene. Resultatene vil være nødvendige for å etablere gode oppfølgings- og behandlingsrutiner for disse pasientene som jo vil ha en oppfølging over mange ti-år. Resultatene av studien vil bli publisert i internasjonale nivå 1 og 2 tidsskrifter og vil bli lagt frem for pasientgruppen i egnede fora. Etterhvert tror vi resultatene vil bli sentrale for å utforme rutiner for oppfølging av disse pasientene. Slik antar vi at studien vil komme pasientene til gode nokså raskt. Hjerte- og karundersøkelsene vil foregå i en forskningsgruppe (Research Group for Clinical Echocardiography) med bred erfaring med hjertesykdom hos kreftpasienter, et fagfelt som nå betegnes kardioonkologi. Ved vår forskningsgruppe ved Kardiologisk avdeling, Oslo universitetssykehus, Rikshospitalet, har vi en rekke studier gående hos pasienter med forskjellige kreftformer. For tiden arbeider 3 PhD stipendiater hos oss innen dette feltet, alle veiledet av Svend Aakhus som er søker for det aktuelle prosjektet. Av disse vil to disputere i 2016 og en i 2017. Til sammen er det publisert mer enn 20 artikler og abstracts fra vår forskningsgruppe innen kardioonkologi de siste 3 årene.
Sluttrapport
Bakgrunn, målsetting og metode
Allogeneic hematopoietic stem-cell transplantation (HSCT) is a potential curative therapy for a variety of malignant or non-malignant diseases. Survival rates have improved in parallel with advances in medical technology and supportive therapies. However, allo-HSCT is a highly intensive and toxic therapy that can lead to late-onset complications that diminish quality of life and at worst shorten life expectancy. Of particular concern is late-onset heart disease due to the use of high-dosages of chemotherapies and acquired cardiovascular risk factors. The aims of this study were to determine the prevalence of heart disease, identify risk factors associated with its occurrence and investigate the relationship between cardiac function and exercise capacity in long-term survivors of allo-HSCT treated in their youth. One hundred and four patients from a nationwide cohort participated in this cross-sectional study. Patients were 17 years of age at transplantation and approximately 35 years old at inclusion. All examinations were performed at Oslo University Hospital by qualified specialists. Methods included clinical examinations, questionnaires, blood tests, echocardiography, spirometry and cardio-pulmonary exercise tests. Cardiac anatomy and function were evaluated with comprehensive echocardiography, which included three-dimensional imaging and speckle-tracking methods. A healthy control population was acquired to compare results from echocardiography and blood chemistry.
Sammendrag
This study was part of the ‘Norwegian Allo-survivorship study’, with the main objectives to identify and evaluated the health aspects and long-term complications in survivors of allo-HSCT treated in as child, adolescents and young adults. Ethical approvals and funding from extra-foundation and cancer foundation was obtained prior to study start. The data collection was extensive and required collaboration and expertise from multiple medical fields. Statistical guidance was obtained throughout the study. This study adhered to the initial aims. All examinations were conducted at Oslo university hospital over a two day stay. Echocardiography was the main method, and was preformed and analyzed by the first author. To increase validity, an adequate sized healthy control group with similar characteristics was obtained. Selection bias was accounted for in statistical comparisons. Measurement bias was reduced by conducting analyses in a random manner and blinded to group and clinical status. Each manuscript underwent peer-review progress that aided and improved the quality of article. All manuscripts were published in credible open-access publications.
Resultater og virkninger
This study found significantly reduced left and right ventricular systolic function in survivors compared to healthy controls. Reductions in ventricular function and signs of remodeling were associated with use of anthracyclines, and seemed to increase in a dose-dependent fashion. Hypertension was found to be associated with reduced longitudinal systolic function of the left ventricle. Pericardium abnormalities found in 8% and mostly limited to chronic GVHD. Reduced exercise capacity was found in 45%, and reduced left ventricular systolic function by global longitudinal strain was independently associated with reduced oxygen-uptake. Overall, the results recommend allo-HSCT survivors receive life-long surveillance that incorporates evaluation of the heart. Health care providers need to act assertive to limit modifiable cardiovascular risk factors, and encourage healthy lifestyles to limit the effects of deconditioning. Echocardiography should be conducted prior, shortly afterwards and at regular intervals during follow-up. Greater surveillance with echocardiography maybe warranted in patients exposed to high-dose chemotherapy and/or in patients with cardiovascular risk factors.