Author + information
- aBrigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
- bDivision of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Muthiah Vaduganathan, Brigham and Women’s Hospital Heart & Vascular Center, 75 Francis Street, Boston, Massachusetts 02115.
During his 2015 State of the Union address, former U.S. President Barack Obama launched the Precision Medicine Initiative, an innovative and ambitious effort to collect genetic and other health data on 1 million individuals nationwide to spur the development of tailored, patient-specific therapies. On December 13, 2016, the former President signed the 21st Century Cures Act into law, securing $4.8 billion in federal funding to further efforts in building a precision medicine infrastructure. This initiative, together with dedicated funding, has promoted interest in personalized approaches to clinical care and research across disciplines of medicine. Targeted biological therapies are now available in the treatment of various lung cancers and leukemia, while pharmacogenomics have enabled the selection of antiretroviral therapies with minimal side-effect profiles for patients with human immunodeficiency virus.
Similar, but more modest, trends toward precision medicine have been observed in cardiology (1,2). Clinically relevant examples include the discovery of common genetic variants affecting the response to certain cardiovascular drugs (e.g., variation in the SLCO1B1 gene influencing rates of statin-induced myopathy, and variation in the CYP2C19 gene contributing to poor clopidogrel metabolism) (3). Further advancements in next-generation sequencing, other “-omic” sciences, and systems biology and network medicine have shifted the focus beyond single genes and have facilitated a broader integrative understanding of biological pathways influencing therapeutic response. Similarly, our ability to capture dynamic patient data with electronic health records (EHR) and mobile health technologies has furthered the promise of personalized clinical approaches. Despite this progress, the application of these resources and information by practicing cardiologists to individualize therapies has been less robust. It is plausible that providing a more structured training environment may better prepare the next generation of cardiologists to understand the role, limitations, and potential of “precision cardiology” and promote its application into mainstream practice. We identify gaps in the current cardiology fellowship paradigm and discuss potential future directions in advancing training in precision medicine.
What Is Precision Medicine and What Makes Cardiology Different?
Precision medicine is an approach to disease management that attempts to improve available therapeutic options for individual patients and patient groups by accounting for variability in genetic background, environment, and behavior. Cardiology poses unique challenges to the successful integration of precision medicine. Many chronic cardiovascular ailments develop over years and may be clinically silent until late in the disease course. Even after clinical presentation, certain cardiovascular traits—such as heart failure with preserved ejection fraction—represent heterogeneous phenotypes that are affected by the complex interplay of numerous genetic, lifestyle, and environmental factors. However, these challenges also present opportunities in cardiovascular medicine for precision medicine approaches to inform all phases of clinical care, from prevention and risk assessment to diagnosis, classification, prognosis, and treatment. Dedicated training, tools, and approaches are thus required in the application of precision cardiology, which may be distinct from those of other medical disciplines.
Moving Toward a “Trainee-Centric” Fellowship Model
The Accreditation Council for Graduate Medical Education, established in 1981, sets basic competencies and minimal fellowship requirements (4), and the American College of Cardiology’s Core Cardiology Training Statement (COCATS) provides more specific targets, goals, and expectations. Overall, these educational bodies have provided a structured framework for the nearly 200 cardiology training programs in the United States, standardizing quality and educational focus. The latest iteration of COCATS made important strides in shifting toward competency-based milestones and introducing more program-level flexibility in meeting these benchmarks (5). In the context of a rapidly changing health care environment and the availability of new tools and resources, individual training programs will need to continue to adapt and tailor these expectations to meet the needs and interests of their fellows. Despite this important evolution in framework, and although COCATS 4 highlights major areas in research and scholarly activity that may complement clinical training (6), there is limited attention to the topic of precision medicine and pathways to operationalize this broad guidance.
Integrating Precision Medicine Into Fellowship Training
Because precision medicine is relevant to a variety of career trajectories within cardiology, we believe it is important that all fellows receive adequate exposure during training. Although a prescriptive, all-encompassing curriculum may be neither pertinent nor feasible during fellowship, a basic set of core competencies should be expected, and may include familiarity with cardiovascular genetics (construct a genetic pedigree, meet with a genetic counselor, interpret a genetic test result), knowledge of EHR-based clinical or research queries, and a fundamental understanding of applied statistics. We propose that fellows tailor precision medicine experiences to complement their respective career tracks (Figure 1). For example, a clinical fellow may leverage the institutional EHR to apply a cardiovascular risk score to his or her ambulatory panel of patients. A fellow pursuing a clinical research pathway may partake in advanced statistical courses in machine-learning to improve phenotyping of a complex syndrome. A fellow interested in health care policy and outcomes may investigate the policy implications of disclosing a patient’s genetic test results, and a budding physician-scientist might explore the pharmacogenomics influencing a patient’s response to a therapeutic agent. Training in precision medicine should be customized to each fellow’s incoming experience and outgoing desired career objectives.
Existing Models of Training in Precision Medicine
There are a number of formalized programs across the United States that offer dedicated training in genomic science and genomic medicine supported by National Human Genome Research Institute institutional training grants (T32). These are typically 2-year training programs that involve a core lecture series, rotations through genomic medicine-focused clinics and laboratories, and a longitudinal research commitment. There is less precedent for ancillary training in precision medicine during residency or other specialty fellowships. Recognizing this gap in medical education, the pathology residency program at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, has developed and successfully implemented a curriculum in genomics and personalized medicine. This pioneering effort includes 3 1-h lectures, a practical component that provides exposure to direct-to-consumer genotyping kits, and a concluding presentation related to genome-wide association studies (7,8).
Cardiovascular Fellowship—Where Is the Time?
New time-intensive curricula may be challenging to integrate into an already busy and often lengthy clinical fellowship. As such, it is essential to embed elements of precision medicine into existing fellowship activities, permitting flexibility with respect to how these expectations are met. Practically, principles of precision medicine (e.g., the strengths and weaknesses of genome-wide association studies and administrative data mining) may be incorporated into routine institutional didactic sessions or local seminar series, or be highlighted at the fellows-in-training tracks at national meetings. Fellows may learn and practice relevant skills in the context of individual clinic patients, for example, conducting a certain number of detailed family/genetic histories over the course of the year. Similar to the precision medicine curriculum created at Beth Israel Deaconess Medical Center, the American College of Cardiology could develop an online educational module/webinar or host dedicated off-site symposia for further training in population genetics, working with large datasets, and the ethical considerations of genetic testing. These adjunctive resources may facilitate education in key precision medicine topics without compromising time from other core competencies. Finally, related didactic coursework or investigative efforts may be pursued during elective rotations or time dedicated to research training during fellowship.
Building a Precision Medicine Training Environment
Successfully incorporating the essentials of precision medicine into current fellowship training models will require aligning interests, interdisciplinary collaboration, and multilevel support. First, at a leadership level, institutions and research organizations will need to continue to build systems to encourage precision medicine. In 2010, Duke University School of Medicine created a dedicated Center for Applied Genomics & Precision Medicine (9), which offers an effective and supportive precision medicine training environment. Key characteristics of Duke’s program and other successful platforms around the United States include: 1) maintenance of interdisciplinary interaction; 2) receipt of longstanding support from institutional leadership; and 3) commitment of resources to support trainee education at all levels, including fellowship. Second, established funding opportunities for fellows interested in pursuing precision medicine-focused research should be made available. Funding may be obtained via institutional pilot grants or content-specific foundation grants. The American Heart Association's Institute for Precision Cardiovascular Medicine offers several grant opportunities available to early-career investigators to pursue pathways in precision cardiology. Finally, cardiovascular journals, such as JACC: Basic to Translational Science and Circulation: Cardiovascular Genetics, are uniquely positioned to involve fellows in the editorial process of reviewing and processing papers related to precision medicine.
The Future of Precision Cardiology: A Measured View
It has been >2 years since the former President’s public endorsement of precision medicine; yet, its optimal implementation remains ill-defined and its promise untested in cardiology. Despite substantial progress in building platforms and advancing techniques and technologies (1,2), a precision cardiovascular approach requires further study, and questions remain regarding feasibility, cost-effectiveness, and downstream effect on cardiovascular clinical outcomes. Ultimately, precision cardiology may only influence a subset of patients, and will need to be complemented by more global preventative and therapeutic efforts (e.g., the polypill or smoking cessation). Despite these uncertainties and although training in precision medicine will require a certain level of restructuring, time, and resource expenditure, we believe this investment is worthwhile. Knowledge and facility with aspects of precision medicine will allow the next generation of cardiologists to not only advance progress toward realizing its promise, but also become stewards of its optimal clinical application.
- Geoffrey S. Ginsburg, MD, PhD ()
RESPONSE: Training in Precision Cardiology
The Time Is Now
We are in the “precision” era of medicine. The practice of precision cardiovascular medicine has great potential to improve quality and effectiveness, and possibly the overall costs of health care, thanks to the advances in genome-based technologies and analytics over the past decade. Despite some great early successes in this field, most of the current generation of clinicians and many PhD researchers are not prepared to take full advantage of the opportunities afforded by these advances in genome-based technologies and data science. National Institutes of Health funding in genetics and genomics has been primarily focused on T1 (discovery) research, and much less on moving those discoveries into clinical practice. Data from the National Cancer Institute (1) and National Heart, Lung, and Blood Institute (2) show that only 2% of funded genetics and genomics grants in 2007 (National Cancer Institute) and 2008 to 2011 (National Heart, Lung, and Blood Institute) are in T2 (human application), T3 (implementation science/dissemination), and T4 (outcomes and population health) research. Our ability to advance genomics into medicine will depend on a workforce that understands how to apply the “genomic medicine toolbox” (3) to clinical problems. In addition, its success will depend on developing a critical mass of clinician-scientists who can review research proposals in genomic medicine, recognize those with outstanding potential, and train the next generation of outstanding cardiovascular investigators.
Training in genomic and precision medicine is increasingly undertaken in the medical specialties where it is currently relevant—pediatrics (due to medical genetics’ focus on Mendelian disorders and rare diseases) or pathology (due to the field’s critical involvement in molecular diagnostics and laboratory testing). However, other areas of medicine, such as cardiovascular medicine, need to be both prepared and able to train their clinicians and scientists to drive this research and clinical agenda by bringing genomics tools to their specialties and knowing how to use them clinically. Even when genomic tests are validated and available, many providers do not use them in clinical practice (4). Cardiovascular genomic medicine research training will create subject matter experts—locally and nationally—who will be catalysts for educating their peers and for the diffusion of genomics into cardiology. At some academic centers, genomic medicine education is taking place already at the point of need or point of decision-making. The Duke Center for Applied Genomics and Precision Medicine, for example, is fortunate to have a novel Genomic Medicine T32 training grant. Consistent with the recommendations of Dr. Vaduganathan and colleagues, our philosophy is to make training flexible and tailored (Figure 2). Also, in the National Human Genome Research Institute’s eMERGE (Electronic Medical Records and Genomics) (5) and IGNITE (Implementing Genomics in Practice) (6) networks, clinical decision support tools are used to help providers understand the meaning of genetic tests and the actions that might be taken with the results.
However, there is a critical need for earlier specialization and skills acquisition for developing the research agenda for clinical applications of genomics in medicine. The major areas of focus for the cardiovascular trainee should be: 1) an understanding of discovery technologies; 2) how to use and analyze the data from these technologies; 3) implementation science; 4) outcomes research; and 5) the policy framework to support adoption. The time is now to help our trainees herald in the next generation of precision medicine.
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- Srinivas P.R.,
- Papanicolaou G.J.,
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- Fabsitz R.R.
- National Human Genome Research Institute
- National Human Genome Research Institute
The authors are supported by postdoctoral training grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (T32 HL 007604 to Drs. Vaduganathan and Qamar; T32 HL 007208 to Dr. Aragam).
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- ↵Duke Center for Applied Genomics & Precision Medicine. Available at:. https://precisionmedicine.duke.edu/. 2872017.
- What Is Precision Medicine and What Makes Cardiology Different?
- Moving Toward a “Trainee-Centric” Fellowship Model
- Integrating Precision Medicine Into Fellowship Training
- Existing Models of Training in Precision Medicine
- Cardiovascular Fellowship—Where Is the Time?
- Building a Precision Medicine Training Environment
- The Future of Precision Cardiology: A Measured View