Academic Center for Cardiac Morphology and Electrophysiology

Last updated: 318 days ago.

Our overall aim is to strive for (improvement of) personalized diagnosis and therapy of atrial fibrillation (AF) and its sequela (e.g. stroke) by implementing fundamental and translational research into daily clinical practice and providing (international recognized) educational programs for (future) healthcare providers, researchers and patients.

Our goals are to

  1. investigate electrical signal morphologies related to genetic/molecular alterations to determine AF stages,
  2. develop biomedical imaging technology guiding AF therapy,
  3. test innovative mapping/ablative tools in our catheterization laboratories,
  4. evaluate AF treatment at dedicated (regional) outpatient clinics focusing on patient centered outcomes,
  5. provide a 24/7 service for diagnosis and therapy of stroke (Rotterdam Stroke Center/Service),
  6. investigate the role of (novel) anticoagulant therapy in preventing ischemic stroke and other arterial thrombotic complications in AF patients,
  7. provide a 24/7 emergency admission service for patients presenting with AF.
Academic Center of Excellence

Research Activities

High resolution, cardiac (body surface) mapping and signal analysis to unravel AF mechanisms, create electrical profiles to early recognize AF onset and progression and to guide patient tailored therapy.
Developing ultrasound, intracardiac, miniature 3D image probes for guiding AF ablation, tools for photoacoustic monitoring of atrial ablation lesion formation and imaging of electromechanical wave propagation.
Evaluation of outcomes of novel diagnostic instruments, (invasive) AF therapies, AF-related heart failure/stroke and anti-coagulation therapy at dedicated (out)patient (regional) clinics to ascertain evidence based care.
Investigation on transcriptome and epigenetic level, combining 4C, DNA methylation, and RNA seq. analysis of blood and tissue samples. Following established bio-informatic pipelines, data sets will be combined with public database information to identify target pathways for further evaluation in vitro models.
Molecular pathophysiology and pharmacology of AF; research on druggable targets, protein quality control systems in animals and humans.
Identification of molecular biomarker profile in circulating cells for AF detection and prediction enabling combination of molecular biology with bio-informatics.
Decipher the role of the microtubule (MT) cytoskeleton in the structural integrity and signaling in the cardiac myocyte, and in malfunctioning myocytes in AF.

Research is performed by doctors, epidemiologists, biologists and engineers in collaboration with industrial partners and e.g. Harvard-, Odense-, Basel-, Seattle-Montreal-, Ohio University (visiting professorships, PhDs exchange programs).

High resolution, cardiac (body surface) mapping and signal analysis to unravel AF mechanisms, create electrical profiles to early recognize AF onset and progression and to guide patient tailored therapy.
Developing ultrasound, intracardiac, miniature 3D image probes for guiding AF ablation, tools for photoacoustic monitoring of atrial ablation lesion formation and imaging of electromechanical wave propagation.
Evaluation of outcomes of novel diagnostic instruments, (invasive) AF therapies, AF-related heart failure/stroke and anti-coagulation therapy at dedicated (out)patient (regional) clinics to ascertain evidence based care.
Investigation on transcriptome and epigenetic level, combining 4C, DNA methylation, and RNA seq. analysis of blood and tissue samples. Following established bio-informatic pipelines, data sets will be combined with public database information to identify target pathways for further evaluation in vitro models.
Molecular pathophysiology and pharmacology of AF; research on druggable targets, protein quality control systems in animals and humans.
Identification of molecular biomarker profile in circulating cells for AF detection and prediction enabling combination of molecular biology with bio-informatics.
Decipher the role of the microtubule (MT) cytoskeleton in the structural integrity and signaling in the cardiac myocyte, and in malfunctioning myocytes in AF.

Research is performed by doctors, epidemiologists, biologists and engineers in collaboration with industrial partners and e.g. Harvard-, Odense-, Basel-, Seattle-Montreal-, Ohio University (visiting professorships, PhDs exchange programs).

Type of

Collaborations

Harvard-, Odense-, Basel-, Seattle-Montreal-, Ohio University

Educational

Contributions

We provide education for Ba and MSc students of medicine, clinical technology, technical medicine, nanobiology, molecular medicine, information technology and clinical training for residents and fellows.

We also regularly participate in Junior Medschool and minors of TU Delft.
Our PIs are involved in PhD students training programs of cardiovascular research schools of EMC (Coeur), VUMC, UMCU and TU Delft, NIHES, 'Papendal' PhD courses on cardiovascular physiology, the EMC Master Clinical Research. They play an active role in international education through proctoring, organizing international congresses and fellow training together with European Societies.

Professors within our ACE also hold chairs at TU Delft and the director of the Cardiovascular Institute of Education (CVOI) of the Dutch Society of Cardiology (NVVC) is connected to our ACE. Quality of our educational programs is continuously being improved by using feedback from visitations by (inter)national organizations. Within our consortia, we provide (young talent) multi-disciplinary and multidimensional educational programs combining clinical, basic and translational research and technical developments, also within the Medical Delta.

At present, our ACE hosts more than 20 international MSc/PhD students and fellows from different countries of Europe, Africa, Asian and United states.

Patient

Care Activities

We treat complex AF adult and pediatric patients with congenital heart disease, advanced heart failure, inherited cardiovascular diseases and serve as tertiary referral center for patients with (multiple) failed therapies.

Protocolized care of AF patients involves emergency care, Rijnmond Region new onset AF-, pre-intervention screening, post-intervention (outpatient)clinics, cathlabs, surgical rooms, AF detection with implantable devices, regional center for anticoagulant therapy for prevention of ischemic stroke and other arterial thrombotic complications and Stroke Center with 24/7 service for personalized diagnosis and therapy of stroke.

Databases register e.g. success rates of AF therapies, associated complications thereby contributing to evidence based care of AF patients and improvement in quality of life or care (e.g. 'meetbaar beter') in addition to outcomes of regular visitations. Current AF therapies are moderately effective and have side-effects. Our research projects contribute to development of diagnostic tools, innovative mapping and imaging tools improving ablative (surgical) therapy, and new insights into genetic and molecular alterations associated with AF enabling development of novel pharmacological therapies.

Our ACE provides a worldwide unique individualized, multi-disciplinary management strategy of AF patients aimed at improving patient outcomes with a continuous feedback on value based health care parameters.

Societal Relevance to Research, Education and Patient Care

In the Netherlands, the total number of new AF patients is 45,085/year; total costs are 583 million euro/year. As our goal is to provide earlier and more effective AF therapy resulting in prevention of AF progression, AF related complications and hence improved patient outcomes, the economical burden will be significantly reduced, the public health will be improved and interventions will be more cost effective.

Dissemination of scientific findings to scientific audience via traditional routes (meetings, publications, consortia networks) and general public via patients/medical specialists interest groups (Hart-Vaat group, NVVC, Dutch Heart Foundation, Atrial Fibrillation Innovation Platform). We are involved in development of http://www.afibmatters.org, a patient education website of the European Heart Rhythm Association. PIs participate(d) in (inter)national consensus documents or guidelines on AF management in patients with congenital heart and inherited cardiovascular diseases, pediatric patients, invasive therapy of AF and stroke guidelines. Multidisciplinary curricula are established by participants of CVON consortia.

PIs have patents on imaging technologies and novel drugs targeting structural remodeling. Further contributions to economic valorization include development of AF biomarkers (early detection and subsequent prevention) via translational pipelines and networks (cooperation interested SMEs), novel mapping and imaging tools guiding AF therapy of AF patients and pharmacological therapies.

Viability of Research, Education and Patient Care

PIs share data with other members (clinicians, engineers and basic scientists) to optimize dataset usage for basic science and translational applications; this is also the case for (inter)national consortia in which PIs participate. There is a dedicated training program to stimulate (young) talented researchers involving different departments/institutions where they receive multidisciplinary training into different research areas.

There is funding to visit international research groups to conduct experiments, learn new technologies or clinical skills and to initiate collaborations. CVs are in this way improved enabling enrollment in personal grant applications/post-doc programs. Most PIs and PhDs (>80%) have international working experience; PIs participate in (clinical) international multicenter studies and guidelines/consensus documents and organize or provide clinical training in collaboration with European societies. PIs are involved in international clinical education by proctoring and we organize international, educational meetings for clinicians and researchers. About 87% of our publications are published in the top 10% ranked journals. PhDs produce at least 5 international peer-reviewed journal publications and about 6 international conference proceedings.

Key and relevant publications of the last five years

  • A randomized trial of intraarterial treatment for acute ischemic stroke. NEJM
  • Electropathological Substrate of Longstanding Persistent Atrial Fibrillation in Patients With Structural Heart Disease Epicardial Breakthrough. Circulation.
  • Front-end receiver electronics for a matrix transducer for 3D transesophageal echocardiography. IEEE Trans Ultrason Ferro Freq Control.
  • Automated Border detection in 3D echocardiography: principles and promises. Eur Heart J of Echocardiography
  • Extended use of dabigatran, warfarin or placebo in venous thromboembolisms. NEJM.
  • An entirely subcutaneous implantable cardioverter-defibrillator. NEJM.
  • Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics.
  • Plus-End-Tracking proteins and their review interactions at microtubule ends. Current Biology.
  • Endothelial cell-specific FGD5 involvement in vascular pruning defines neovessel fetal mice. Circulation.
  • Dynamic Microtubules Catalyze Formation of Navigator-TRIO Complexes to Regulate Neurite Extension. Curr Biol.

PhD theses of the last five years

  • Newly-diagnosed disturbed glucose metabolism after TIA or stroke. Fonville S.
  • Atrial Fibrillation: to Map or Not to Map ? Yaksh A.
  • Optimizing safety and efficacy of catheter ablation procedures. Akca F.
  • Augmenting electrophysiology interventions with advanced 3D transesophageal echocardiography. Haak A.
  • Low-power receive-electronics for a miniature 3D ultrasound probe. Zilli Y.
  • Effects and outcome of hemostatic treatment in bleeding disorders.
  • Atherosclerosis: from bench to bedside. Den Dekker W.
  • Structural remodelling associated with atrial fibrillation. D. Zhang
  • Functional analysis of CTCF and CTCFL. W. Soochit.
  • Loss of proteasis as a substrate for atrial fibrillation,defining novel targets for therapy.

Non-scientific publications related to the ACE