As exciting advances are made in the world of medicine and new therapies
become available to treat cardiovascular diseases, there is an increasing
need to validate their safety and maximize their benefit for patients. The
Smith Center’s mission is to apply the highest standard of scientific
evaluation to essential questions in cardiovascular medicine. We combine
novel analytical approaches with deep clinical expertise to understand and
improve patient outcomes and advance healthcare delivery.
The Smith Center works within three main areas of focus:
Assessing real-world comparative effectiveness of treatment strategies,
medications and devices;
Evaluating ethical concerns in medicine as well as the intended and
unintended consequences of health policy interventions;
Assessing the ability of novel sources of data (i.e. “Big Data”) to
improve risk stratification of patient illness and enhance personalized
approaches to medical care.
The projects listed below are a sample of
our current research.
Comparative Effectiveness Research
Modern medicine has given rise to an abundance of different ways to treat
chronic diseases, and as such, it is increasingly important to understand
how these treatment strategies compare to one another in order to maximize
efficacy and safety.
Rigorous Statistical Methods
A major focus of the research at the Smith Center is to evaluate the effectiveness, benefits and potential harms of different cardiovascular treatments and technologies using state-of-the-art statistical methods. Dr. Daniel Kramer and collaborators at Harvard University found high variability among health-care facilities in their use of cardiac resynchronization therapy devices with (CRT-D) and without (CRT-P) defibrillator backup. Although most patients receive the more costly CRT-D device, this study, which used instrumental variable analysis to control for confounding variables, suggested that CRT-P devices may be preferable for many patients owing to relatively lower costs and lower complication rates associated with the devices.
Kramer DB, Normand ST, Volya R, Hatfield LA. Facility-Level Variation and Clinical Outcomes in Use of Cardiac Resynchronization Therapy With and Without an Implantable Cardioverter-Defibrillator. Circulation: Cardiovascular Quality and Outcomes. 2018;11:e004763.
We use real world data to understand the best ways to allocate resources to positively impact patient outcomes. Recent work in this area includes looking at the costs associated with PCSK9 inhibitors used to control cholesterol. The Smith Center recently recruited Dr. Dhruv Kazi from the University of California, San Francisco, to serve as the Center's Associate Director. An expert health economist and cardiologist, he has also published on costs associated with PCSK9 inhibitors.
Hess GP, Natarajan P, Faridi KF, Fievitz A, Valsdottir L, Yeh RW. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapy: Payer Approvals and Rejections, and Patient Characteristics for Successful Prescribing. Circulation. 2017 Dec 5;136(23):2210-2219.
Kazi DS, Penko J, Coxson PG, Moran AE, Ollendorf DA, Tice JA, Bibbins-Domingo K. Updated Cost-effectiveness Analysis of PCSK9 Inhibitors Based on the Results of the FOURIER Trial. JAMA; 2017.
Kazi DS, Penko J, Coxson PG, Guzman D, Wei PC, Bibbins-Domingo K. Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Ann Intern Med; 2019 Jan 1.
Measurement of Patient-Reported Outcomes
We are developing innovative ways to measure patient-reported outcomes in the routine course of clinical care in order to
evaluate the effectiveness of interventions primarily meant to
improve patient symptoms.
Blumenthal DB, Strom JB, Valsdottir LR, Howard SE, Wagle NW, Ho KH, Horn D, OKeefe SM, Wasfy JH, Metlay JP, Yeh RW. Patient Reported Outcomes in Cardiology: A Comparison of Two Programs to Assess Angina Burden in Coronary Artery disease. Circulation: Cardiovascular Quality and Outcomes. 5 Nov 2018;11:e004794.
Health Policy and Ethics
A key area of focus at the Smith Center is ethical issues relating to
medical practice. Our current research is examining topics that include
medical decision-making, device implantation and removal, and end-of-life
issues, and extends to include the impact of government policy on patient
The implementation of the Affordable Care Act brought changes to
the way hospitals are reimbursed by Medicare and Medicaid, such
that hospitals are financially penalized for having high readmission rates. Researchers at the Smith Center are using large
national datasets to investigate the impact of this policy on hospital performance and patient outcomes.
Wadhera RK, Joynt Maddox KE, Wasfy JH, Haneuse S, Shen C, Yeh RW. Association of the Hospital Readmissions Reduction Program With Mortality Among Medicare Beneficiaries Hospitalized for Heart Failure, Acute Myocardial Infarction, and Pneumonia. JAMA. 2018;320(24):2542-52.
Wasfy JH, Zigler CM, Choirat C, Wang Y, Dominici F, Yeh RW. Readmission Rates After Passage of the Hospital Readmissions Reduction Program: A Pre–Post Analysis. Annals of Internal Medicine. 2017;166(5):324-31.
Medical Device Regulation and Surveillance
A growing number of implantable devices, such as pacemakers and
implantable cardioverter defibrillators (ICDs) now contain remote
monitoring systems that connect patients to clinicians and
manufacturers. In addition, large registries of patients with implanted devices are being organized to more
quickly identify emerging safety issues. However, intensive collection of personal data
through continuous remote monitoring and device registries
implicates patients’ privacy interests. Smith Center researchers seek to define and evaluate the ethical challenges related to information sharing and digital connectivity. Dr. Daniel Kramer, Smith Center researcher and electrophysiologist, has a deep interest in ethics and regulatory matters and has published widely in this area.
Wann D, Waks JW, Kramer DB. Clinical and regulatory considerations for novel electrophysiology mapping systems: Lessons from FIRM. Pacing Clin Electrophysiol. 2018 Sep 25
Kramer DB, Lo B, Russo RJ. Implications of Medicare Coverage for Magnetic Resonance Imaging in Patients With Capped or Epicardial Leads. JAMA Cardiol. 2018 Nov 14.
Public Reporting of PCI Outcomes
Several states have implemented policies in recent years that
mandate public reporting of patient outcomes for certain
procedures, including percutaneous coronary intervention. The Smith
Center is researching the impact of these policies on practitioner
risk avoidance and subsequent effects on patient outcomes.
A recent study led by Dr. Rishi Wadhera suggested that policy efforts to reduce inappropriate use of percutaneous coronary intervention (PCI) procedures may have inadvertently led physicians to change their coding practices.
Wadhera RK, Sukul D, Secemsky EA, Shen C, Gurm HS, Boden WE, Yeh RW. Temporal Trends in Unstable Angina Diagnosis Codes for Outpatient Percutaneous Coronary Interventions. JAMA Internal Medicine. Published online December 17, 2018.
The Smith Center aims to examine novel sources of data, and to analyze
existing data in new ways that support personalized approaches that account
for the diversity of patient responses to treatment.
Risk Prediction Modeling and Personalized Medicine
Researchers at the Smith Center are developing and testing new
technologies to predict individual patients’ risk of adverse events
after cardiac procedures based on data from the Electronic Health Record and other administrative data sources. Harun Kundi, MD, a visiting international scholar at the Smith Center, has recently published a series of studies which showed that incorporating non-traditional markers of frailty to traditional risk scores can improve the prediction of outcomes such as mortality after transcatheter valve procedures.
Kundi H, Popma JJ, Valsdottir LR, Shen C, Faridi KF, Pinto DS, Yeh RW. The Value of Claims-Based Nontraditional Risk Factors in Predicting Long-term Mortality After MitraClip Procedure. Canadian Journal of Cardiology. 2018 Dec;34(12):1648-1654.
Kundi H, Valsdottir LR, Popma JJ, Cohen DJ, Strom JB, Pinto DS, Shen C, Yeh RW. Impact of a Claims-Based Frailty Indicator on the Prediction of Long-Term Mortality After Transcatheter Aortic Valve Replacement in Medicare Beneficiaries. Circ Cardiovasc Qual Outcomes. 2018 Oct;11(10):e005048.
Identification of Heterogeneous Treatment
Because patients differ from one another in their responses to
treatment, identifying those patients who have the greatest opportunity to benefit
as well as those with the least to gain from medical interventions
is essential for high quality, cost-effective, patient-centered
care. Smith Center investigators have a number of projects devoted
to understanding heterogeneous treatment effects across a broad
spectrum of cardiovascular conditions.
In particular, the team is working on a large NIH R01-funded study with a consortium of investigators to validate the use of real world claims and registry data in the evaluation of medical therapies in representative populations.