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- Jillianne Code, PhD∗ ()
- ↵∗Department of Curriculum and Pedagogy, 2125 Main Mall, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
At the recent 15th annual Cardiovascular Clinical Trialist forum held in Washington, DC, I was one of several expert panelists to be asked to look into the crystal ball, to look into the future of clinical trials in heart failure. The panelists were doctors or physician-scientists who specialize in heart failure and they are the individual who design, develop, and run large clinical trials.
I am also a doctor, albeit a doctor of philosophy in educational psychology so I had no problem following discussions of sample sizes, p values, control groups, placebos, and outcome measure although, the main outcomes measured in clinical trials are cardiovascular death or all-cause mortality—outcomes I never personally study in my own research. However, I would argue that I have studied these outcomes using a PhD of a different kind, one that specializes in the lived experience of heart failure, because I survived it, from diagnosis through to the end stages and beyond. I am a case study of heart failure (1); I am a clinical trial of one.
To illustrate, I present to you my own case as directly and simply as I can.
After weeks of illness and 3 misdiagnoses of pneumonia, as a 27-year-old woman, I presented to the emergency room (ER) with an ejection fraction (EF) of <10%. The cardiologist on call diagnosed me with idiopathic-dilated cardiomyopathy, and gave me 72 h to live, I was started on the latest medical therapy, and the cardiologist contacted the heart transplantation team. Thankfully, I responded to medical therapy; and 20 lbs of fluid were removed by diuresis. After my initial diagnosis, I recovered to an EF of 40% and remained stable for 4 years. At the age of 33, I had sudden onset of stroke, followed by a second stroke, was mis-diagnosed with anxiety in the ER, and was administered Ativan (Pfizer, New York, New York). When sent home, I had lost the ability to use my right arm and developed aphasia. On follow-up with my heart failure team, an echo revealed a clotted heart and an EF of 28%. Shortly thereafter, I was fitted with an implantable cardioverter-defibrillator, I regained the use of my right arm and the aphasia improved and I was stable for another 3 years with the addition of warfarin to my medical regimen.
At the age of 37, I suddenly experienced a marked reduction in my ability to walk, climb stairs, and I developed severe dyspnea, and edema in my ankles and mid-section. A follow up echo revealed an EF of 13%; I was hospitalized, evaluated, listed for cardiac transplantation, and administered inotropes. Seven months later, I had a further reduction in daily functioning and I experienced severe cognitive impairment. I was hospitalized with inotrope therapy, and was referred for emergency left ventricular assist device (LVAD) implantation (Figure 1) as a bridge to transplantation using a minimally invasive procedure (2). While recovering from LVAD surgery, I developed severe gastrointestinal bleeding. Bolus blood products were administered, and I was moved to the cardiac intensive care unit (CICU). Computed tomography revealed the bleeding source in the cecum and I underwent emergency vascular surgery to cauterize the bleeding when 1 coil was placed. Less than 24 h later, gastrointestinal bleeding returned, bolus blood products were administered again, and I underwent emergency surgery for a second cauterization and coil placement. A further 24 h later, bleeding began again, and a general surgeon was brought in to discuss the possibility of removing the offending bowel section. Thankfully, the bleeding slowed and stopped on its own, I recovered over the next week and was discharged.
Seven months following LVAD surgery, I underwent orthotopic heart transplantation on October 8, 2014. I was kept in a coma for 8 days due to unstable blood pressure, infection, and low kidney and liver function. On the eighth day, I became stable enough to attempt awakening. Unfortunately, I awoke with severe delirium and muscle atrophy, over the next weeks my recovery was slow and I had to learn how to feed myself and walk again. The pathology on my original heart revealed chronic active myocarditis (Figure 2).
Two years post-transplantation, I started having upwards of 20 heart attack−like pains day and night. After undergoing provocative angiography in March 2017, with no blockages revealed, I was diagnosed with coronary vasospasm something rarely reported in the literature on heart transplant patients (2). Nine months later that year, still with the same number of pain episodes that I managed mainly with nitroglycerin spray, I had a heart attack on December 26. An emergency catheterization revealed severe cardiac allograft vasculopathy with all arteries 80-100% blocked. I received a series of stents in my right circumflex artery (a full metal jacket), followed days later by an experimental procedure to open my left circumflex artery (a second full metal jacket). I was subsequently listed for emergency re-transplantation, and after waiting 2 weeks, I underwent a second heart transplantation on January 23, 2018 (1).
So, you see, I am a clinical trial, even though I may be a zebra and have my own phenotype—the outcome of my trial is still unknown although, arguably cardiovascular mortality is something I know quite well. There are many unknowns in heart failure, and even more post heart transplant despite being given the best possible evidence-based care throughout my journey the kind of evidence I needed most has not been enough; for many patients with heart failure this remains true. I celebrate that, for now, I am stable, hopeful, humbled, and motivated into action through advocacy by co-founding the HeartLife Foundation of Canada (http://heartlife.ca). I do this in hopes of making life better for the people that come after me. As clinicians, researchers, and trialists you can learn a lot from me. Not just from my body, my blood, the pathology of my hearts (since I've had 3 now), but my experience. You see, I am the primary end point. I am the outcome. I've surpassed cardiovascular death. I am not just one event as my story illustrates, so your clinical trial does not even begin to tell my story, or that of most patients.
So, as trialists, what can you do? I have given this a lot of thought over the past few years as my hearts were failing, and my drive for advocacy for heart failure grew. First, simply ask patients to be engaged. Invite patients into the conversation by having a conversation with them, you may be surprised by what they say, and the insight in which they say it. Collaborate with patients from project inception, writing grant proposals, through the process of recruitment, data collection, analysis, and dissemination. I would hazard it will make you rethink how you do your work and, you may change or add to the questions that you ask in your trial designs. Second, include patient reported outcomes in your trial design. A reasonable place to start would be to use the Kansas City cardiomyopathy questionnaire, since the Food and Drug Administration has now approved it for use (3,4). Third, reduce the number of requirements for admittance to trials, including better representation of women, visible minorities, indigenous peoples, and individuals of various ages. As a researcher, I understand the statistical complexity of having more variables to account for, but as a patient I also recognize that the validity of a trial is of equal value. Otherwise, consider studying one of the under-represented populations I mentioned even if these trials confirm existing findings, there is an equal probability that they will reveal something unique in these populations that has not been considered. Finally, and perhaps most importantly, have a multidisciplinary team. Engage with social scientists as well as activated patients, and develop trials in which parallel and secondary social science studies are enabled. Imagine the impact of a trial that reveals not only statistical significance but socially valid as well. With the addition of social science evidence and data upon which you can triangulate trial data, the validity likelihood your work increases to the point that it will provide real world context and immediate clinical insight that benefits all stakeholders, especially those that need it the most—the patient.
I am a researcher, a patient, a survivor, a person with lived experience of heart failure—I am your crystal ball. What you can learn from me, from people with lived experience, can be measured and reported. By listening and studying our lived experience your research will enable the showing of a complete picture of heart failure that not only sheds light on future treatments and perhaps even a cure for heart failure, but provides hope and returns agency to people like me, and helps turn heart failure into heart life.
Please note: This article is based on a talk given at the Cardiovascular Clinical Trialist (CVCT) Forum on December 1, 2018 in Washington, DC. Dr. Code has reported that she has no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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- ↵Food and Drug Administration. Medical device development tool (MDDT) qualification summary for the Kansas City cardiomyopathy questionnaire (KCCQ). 2016. Available at: http://bit.ly/FDAKCCQ. Accessed December 20, 2018.