To enable the preservation of cardiac function through the lifetime, several research lines work closely together within CVC (historically organized as CVC-1: clinical heart failure; CVC-2: experimental heart failure; CVC-2: atrial fibrillation). The central theme is safeguarded by including a temporal interaction and translational focus in all research activities. The program of CVC includes the following main aspects:
Standing research lines
1. To study the dynamics of heart disease and its development, our research group makes use of large biobanks, comprising several cohorts of subjects from the general population (PREVEND, LifeLines) with long-term follow-up. These databases often are coupled to other large databases (see Section 7.5 on collaborations), which together will enable the study of components and risk factors for heart disease development. Additionally, we have created and continuously build new large databases of both low-risk and high-risk patients, e.g. patients with new onset HF (PREVEND), and new onset AF (AF risk, RACE 3 and 5) that allow early intervention studies, as well as patient at risk to develop HF (carriers of pathogenic mutations, and post-MI patients (CardioLines), and they are sampled at multiple stages during the CV disease continuum.
2. CVC has a longstanding history of elucidating specific pathophysiological mechanisms that contribute to the onset and progression of HF, which we aim to discover, unravel and describe in a preclinical research program (CVC program 2), situated in the division of experimental cardiology. In recent decades, this has resulted in several new clinical insights, which have been successfully translated into clinical research lines. Several of those were followed by clinical targeted randomized intervention studies. Examples of characteristic, collaborative and world-leading research lines in HF, initiated in experimental studies, with their respective clinical trials are: erythropoietin in HF (RCTs: HEBE, RED-HF), cardiorenal mechanisms (RCT: ARIANE-HF, diuretic resistance studies in PROTECT), diabetes and the use of metformin (GIPS-III), galectin-3, microvascular function (thrombosuction), and genetics in HF. For AF, we are world opinion leaders in mechanisms associated with AF progression and optimal therapy, including rate versus rhythm control (RACE 1&2), optimal pharmacological therapy to prevent AF (VERDICT, CONVERT), and the role of microvascular function and genetics in AF (AF Risk, RACE V).
3. During the last decade, CVC has devoted considerable efforts to establishing genetic consortia that have resulted in much larger databases that have had major impact due to their such stronger power, not only on initiation of both epidemics but also at progression of HF and AF and their associated morbidities and mortality. Furthermore, CVC has successfully obtained funding for national study groups of monogenetic inheritable cardiomyopathies (PREDICT, DOSIS), that ensure strong national embedding. Using detailed phenotyping in combination with genotyping and advanced system biology analyses we will gain better understanding of mechanisms of both initiation and progression of both HF and AF. For specific collaborations and consortia: see the section on national and international collaboration. We will continue to develop and expand these experimental and clinical research lines in clinical HF and AF, but will also expand to pulmonary hypertension, pregnancy and heart disease, and consequences of acute myocardial infarction. These lines will entail pharmacological studies, disease management studies, imaging studies and device therapy.
4. HF and AF are typical diseases of the elderly patient. However, both diseases develop nowadays at younger ages in part due to adverse lifestyle changes, such as obesity and sedentary lifestyle. Our research group will continue to conduct research on the prevalence, predictive value, and cause of co-morbidities in elderly, but also at younger ages, and thereby contribute to healthy ageing of the aging population and the population as a whole. Examples of programs in HF research are HF and diabetes, liver function abnormalities, renal dysfunction, and cognitive dysfunction, with experimental and clinical research lines. For AF, lifestyle changes including physical activity and weight reduction are and will be strongly incorporated in our treatment strategy as currently investigated in RACE 3 (data expected in 2018) and our atrial ablation studies (Cryo and hybrid ablation registries).
5. We lead several large scale HF biomarker studies that are expected to uncover promising novel markers (COACH, BIOSTAT-CHF, CVON-ARENA, PREVEND, PROTECT, CTMM MARC, CardioLines), allowing the study of genetic and plasma biomarkers. We aim to use these to study underlying pathophysiological mechanisms, to predict response both to pharmacological and non-pharmacological therapies, as well as to identify patients at higher risk. We envision working along the translational axis, i.e. from experimental work into the clinic or the reverse (from clinical observations back to mechanistic insights). Also for AF, through the study of genetic and plasma biomarkers, including systems biology analyses, we aim to identify novel targets for atrial fibrillation treatment. Furthermore, RACE V will study the presence and importance of vascular dysfunction and thrombosis in AF in a large cohort of early onset AF patients who will be continuously monitored by a miniaturized implantable loop recorder.
6. We have initiated several large scale AF studies to uncover mechanisms of AF progression, with a special focus on the association between HF and AF, and the discovery of new therapies directed at the underlying mechanisms. The latest trial is VIP-HF, which studies arrhythmogenesis and causes of death in patients with HFpEF and AF.
7. In patients with congenital heart disease, abnormal loading conditions commonly result in heart failure. The Center of Congenital Heart Disease of the CVC conducts research in children and adults with congenital heart disease, focusing on lifetime myocardial and pulmonary vascular adaptation to abnormal loading conditions. Major research subjects are pulmonary hypertension and pulmonary vascular remodeling; right ventricular adaptation and failure; and pregnancy in women with congenital heart disease. We strive to synchronize and merge these efforts with the main research lines, and they are executed in shared laboratory spaces.