This group performs regulatory science research to improve the prediction of which patients will benefit from heart devices and therapies and which patients are likely to be harmed.
Three major areas of application for this research are:
- defining better patient selection criteria for cardiac resynchronization therapy (a special pacemaker for patients with heart failure) and implantable defibrillators,
- developing and testing novel biomarkers for heart toxicity, and
- using patient-specific induced pluripotent stem cell derived cardiomyocytes to predict personalized response to drugs.
Simulation of a left bundle branch block case (impairment of the normal cardiac excitation pathway): anatomical model and corresponding electrocardiogram.
Intracellular calcium transients in contracting adult rabbit heart cell imaged with confocal microsopy.
Arrhythmias detected in human induced pluripotent stem cell derived cardiomyocytes measured with a voltage-sensitive dye.
To this end, the group uses a translational medicine approach including:
- whole heart and single cell cardiac models for medical devices safety and efficacy evaluation,
- assessment of patient-specific induced pluripotent stem cell derived heart cells in precision medicine,
- assessment of human induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias,
- preclinical computational modeling/simulation,
- patient studies to characterize individual patient characteristics,
- individual-patient meta-analyses of clinical trials, and
- post-market outcomes and comparative effectiveness research.
These diverse projects across different translational medicine areas are active collaborations with several researchers, both within the FDA and worldwide.
This research directly impacts the regulatory mission of the agency affecting:
- FDA guidance documents and action plans,
- acquired knowledge that supports pre-market submission reviews,
- achieving the right balance between pre-market/post-market data collection,
- disseminating science to improve the awareness of personalized medicine and facilitate innovative future products and methods,
- development of new biomarkers, and
- improvement of patient care in daily clinical settings.
Ksenia Blinova, Ph.D.
David G. Strauss, M.D., Ph.D.
Loriano Galeotti, Ph.D.
Richard Gray, Ph.D.
Lars Johannesen, Ph.D
Robbert Zusterzeel, M.D., Ph.D.
Johns Hopkins University
University of Rochester
Yale School of Medicine
American College of Cardiology
University of Colorado
Centers for Medicare & Medicaid Services
Karolinska Institutet and Karolinska University Hospital
University of Zaragoza
Spaulding Clinical Research
Cellular Dynamics International
Stem Cell Theranostics
- Human induced pluripotent stem cells
- Primary animal isolated heart cells
- Perfused cardiac tissue/whole heart models
- Optical recordings of membrane potential, intracellular calcium and contractions in monolayers and single cardiomyocytes
- High-throughput microelectrode array recordings from cardiac cells
- Electrical stimulation, pacing, defibrillation
- Modeling and simulation of cardiomyocyte action potentials and electrocardiograms
- ECGLib / ECGLab
Relevant standards & guidance
- Evaluation of Sex-Specific Data in Medical Device Clinical Studies
- FDA Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data
Selected peer review publications
Johannesen et al. Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial. Clin Pharmacol Ther. 2016.
- Vicente et al. Comprehensive T wave Morphology Assessment in a Randomized Clinical Study of Dofetilide, Quinidine, Ranolazine, and Verapamil. Journal of the American Heart Association, 2015
- Zusterzeel et al., Cardiac resynchronization therapy in women versus men: observational comparative effectiveness study from the National Cardiovascular Data Registry, Circulation: Cardiovascular Quality and Outcomes, 2015
- Blinova et al., Assessing Proarrhythmic Potential of Drugs Using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes and Optical Recordings with Voltage-Sensitive Dyes, Circulation Research, 2015
- Johannesen et al., Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil, Clinincal Pharmacology and Therapeutics, 2014
- Blinova et al., Acute effects of nonexcitatory electrical stimulation during systole in isolated cardiac myocytes and perfused heart, Physiological Reports, 2014
- Zusterzeel et al., Cardiac resynchronization therapy in women: US Food and Drug Administration meta-analysis of patient-level data, JAMA Internal Medicine, 2014
- Loring et al., Left bundle branch block predicts better survival in women than men receiving cardiac resynchronization therapy: long-term follow-up of ∼ 145,000 patients, JACC: Heart Failure, 2013
- Johannesen et al., Improving the assessment of heart toxicity for all new drugs through translational regulatory science, Clinical Pharmacology and Therapeutics, 2014
- Galeotti et al., Evaluating strict and conventional left bundle branch block criteria using electrocardiographic simulations, Europace, 2013