The Role of Genetic Testing in the Evaluation of Dilated Cardiomyopathies.

We present an adolescent African American male admitted to the cardiac intensive care unit with cardiogenic shock and acute respiratory failure. Through an overview of his presentation, diagnostic workup, and treatment, we demonstrate the clinical utility of genetic testing in the evaluation of unexplained dilated cardiomyopathies.

COVID-19: Understanding Inter-Individual Variability and Implications for Precision Medicine.

Coronavirus disease 2019 (COVID-19) is characterized by heterogeneity in susceptibility to the disease and severity of illness. Understanding inter-individual variation has important implications for not only allocation of resources but also targeting patients for escalation of care, inclusion in clinical trials, and individualized medical therapy including vaccination. In addition to geographic location and social vulnerability, there are clear biological differences such as age, sex, race, presence of comorbidities, underlying genetic variation, and differential immune response that contribute to variability in disease manifestation. These differences may have implications for precision medicine. Specific examples include the observation that androgens regulate the expression of the enzyme transmembrane protease, serine 2 which facilitates severe acute respiratory syndrome coronavirus 2 viral entry into the cell; therefore, androgen deprivation therapy is being explored as a treatment option in males infected with COVID-19. An immunophenotyping study of COVID-19 patients has shown that a subset develop T cytopenia which has prompted a clinical trial that is testing the efficacy of interleukin-7 in these patients. Predicting which COVID-19 patients will develop progressive disease that will require hospitalization has important implications for clinical trials that target outpatients. Enrollment of patients at low risk for progression of disease and hospitalization would likely not result in such therapy demonstrating efficacy. There are efforts to use artificial intelligence to integrate digital data from smartwatch applications or digital monitoring systems and biological data to enable identification of the high risk COVID-19 patient. The ultimate goal of precision medicine using such modern technology is to recognize individual differences to improve health for all.

Rationale and design of the TAILOR-PCI digital study: Transitioning a randomized controlled trial to a digital registry.

BACKGROUND: Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) is the largest cardiovascular genotype-based randomized pragmatic trial (NCT#01742117) to evaluate the role of genotype-guided selection of oral P2Y12 inhibitor therapy in improving ischemic outcomes after PCI. The trial has been extended from the original 12- to 24-month follow-up, using study coordinator-initiated telephone visits. TAILOR-PCI Digital Study tests the feasibility of extending the trial follow-up in a subset of patients for up to 24 months using state-of-the-art digital solutions. The rationale, design, and approach of extended digital study of patients recruited into a large, international, multi-center clinical trial has not been previously described. METHODS: A total of 930 patients from U.S. and Canadian sites previously enrolled in the 5,302 patient TAILOR-PCI trial within 23 months of randomization are invited by mail to the Digital Study website (http://tailorpci.eurekaplatform.org) and by up to 2 recruiting telephone calls. Eureka, a direct-to-participant digital research platform, is used to consent and collect prospective data on patients for the digital study. Patients are asked to answer health-related surveys at fixed intervals using the Eureka mobile app and or desktop platform. The likelihood of patients enrolled in a randomized clinical trial transitioning to a registry using digital technology, the reasons for nonparticipation and engagement rates are evaluated. To capture hospitalizations, patients may optionally enable geofencing, a process that allows background location tracking and triggering of surveys if a hospital visit greater than 4 hours is detected. In addition, patients answer digital hospitalization surveys every month. Hospitalization data received from the Digital Study will be compared to data collected from study coordinator telephone visits during the same time frame. CONCLUSIONS: The TAILOR-PCI Digital Study evaluates the feasibility of transitioning a large multicenter randomized clinical trial to a digital registry. The study could provide evidence for the ability of digital technology to follow clinical trial patients and to ascertain trial-related events thus also building the foundation for conducting digital clinical trials. Such a digital approach may be especially pertinent in the era of COVID-19.