Leveraging electronic health records for clinical research.

Electronic health records (EHRs) can be a major tool in the quest to decrease costs and timelines of clinical trial research, generate better evidence for clinical decision making, and advance health care. Over the past decade, EHRs have increasingly offered opportunities to speed up, streamline, and enhance clinical research. EHRs offer a wide range of possible uses in clinical trials, including assisting with prestudy feasibility assessment, patient recruitment, and data capture in care delivery. To fully appreciate these opportunities, health care stakeholders must come together to face critical challenges in leveraging EHR data, including data quality/completeness, information security, stakeholder engagement, and increasing the scale of research infrastructure and related governance. Leaders from academia, government, industry, and professional societies representing patient, provider, researcher, industry, and regulator perspectives convened the Leveraging EHR for Clinical Research Now! Think Tank in Washington, DC (February 18-19, 2016), to identify barriers to using EHRs in clinical research and to generate potential solutions. Think tank members identified a broad range of issues surrounding the use of EHRs in research and proposed a variety of solutions. Recognizing the challenges, the participants identified the urgent need to look more deeply at previous efforts to use these data, share lessons learned, and develop a multidisciplinary agenda for best practices for using EHRs in clinical research. We report the proceedings from this think tank meeting in the following paper.

EVEREST II randomized clinical trial: predictors of mitral valve replacement in de novo surgery or after the MitraClip procedure.

OBJECTIVE: The Endovascular Valve Edge-to-Edge Repair Study (EVEREST II) is a prospective, multicenter, randomized controlled trial comparing percutaneous repair with the MitraClip device to mitral valve (MV) surgery in the treatment of mitral regurgitation. The present study analyzed the patient characteristics and treatment effects on mitral repair versus replacement. METHODS: Of 279 patients enrolled, 80 surgical patients underwent 82 MV operations and 178 underwent an initial MitraClip procedure, of whom 37 underwent a subsequent MV operation within 1 year of their index the MitraClip procedure. A logistic regression model was used to predict MV replacement according to valve pathology, etiology of mitral regurgitation, age, previous cardiac surgery, and treatment group. RESULTS: The rate of percutaneous or surgical MV repair at 1 year was 89% (158/178) in patients initially receiving the MitraClip device versus 84% (67/80) in the surgical patients (P = .36). Surgical repair was performed after the MitraClip procedure in 20 (54%) of 37 patients (P < .001 vs surgery). In both the MitraClip device and surgery groups, MV replacement was significantly associated with anterior leaflet pathology (P = .035). Logistic regression analysis showed that anterior leaflet pathology predicted MV replacement. In 5 (13.5%) of 37 patients undergoing surgery after MitraClip therapy, replacement was performed in part because of MV injury associated with the MitraClip procedure. CONCLUSIONS: These data suggest that anterior leaflet pathology is strongly associated with MV replacement in patients undergoing either de novo MV surgery or surgery after MitraClip therapy. MitraClip therapy has a repair rate similar to surgery through 1 year but also imparts a risk of replacement of a potentially repairable valve.

The ABCD (Alternans Before Cardioverter Defibrillator) Trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention.

OBJECTIVES: Because risk stratification with electrophysiological study (EPS) improves efficiency but is invasive, we sought to determine whether noninvasive microvolt T-wave alternans (MTWA) testing could identify patients who benefit from implantable cardioverter-defibrillators (ICDs) as well as EPS. BACKGROUND: Prevention of sudden cardiac death on the basis of left ventricular ejection fraction (LVEF) alone is inefficient, because most ICDs never deliver therapy. METHODS: The ABCD (Alternans Before Cardioverter Defibrillator) trial is a multicenter prospective study that enrolled patients with ischemic cardiomyopathy (LVEF < or =0.40) and nonsustained ventricular tachycardia. All patients underwent MTWA and EPS. ICDs were mandated if either test was positive. RESULTS: Of 566 patients followed for a median of 1.9 years, 39 (7.5%) met the primary end point of appropriate ICD discharge or sudden death at 1 year. As hypothesized, primary analysis showed that MTWA achieved 1-year positive (9%) and negative (95%) predictive values that were comparable to EPS (11% and 95%, respectively). In addition, secondary analysis showed that at the pre-specified 1-year end point, event rates were significantly higher in patients with both a positive MTWA-directed strategy (hazard ratio: 2.1, p = 0.03) and a positive EPS-directed strategy (hazard ratio: 2.4, p = 0.007). Moreover, the event rate in patients with both negative MTWA test and EPS was lower than in those with 2 positive tests (2% vs. 12%; p = 0.017). CONCLUSIONS: The ABCD study is the first trial to use MTWA to guide prophylactic ICD insertion. Risk stratification strategies using noninvasive MTWA versus invasive EPS are comparable at 1 year and complementary when applied in combination. Strategies employing MTWA, EPS, or both might identify subsets of patients least likely to benefit from ICD insertion. (Study to Compare TWA Test and EPS Test for Predicting Patients at Risk for Life-Threatening Heart Rhythms [ABCD Study]; NCT00187291).

Outcome of women versus men with ventricular tachyarrhythmias treated with the implantable cardioverter defibrillator.

INTRODUCTION: Important sex differences in the incidence and outcome of patients with ischemic heart disease, the leading cause of ventricular tachyarrhythmias, have been identified. Implantable cardioverter defibrillator (ICD) therapy has become the treatment of choice for patients with ventricular tachycardia (VT) and ventricular fibrillation (VF), but little is known about gender differences in the outcome of ICD-treated patients. METHODS AND RESULTS: In this retrospective study, we compared arrhythmic events and survival of 376 women and 1,654 men treated with an ICD as part of prospective evaluations of transvenous devices or lead systems. Women were younger (62+/-14 years vs 65+/-12 years, P = 0.0005), had higher left ventricular ejection fraction (0.36+/-0.15 vs 0.32+/-0.13, P < 0.0001), were more likely to present with VF (34% vs 19%, P < 0.001), and had lower implantation defibrillation threshold (11+/-6 vs 13+/-6 J, P < 0.0001). Implant complication rates were similar in men and women (2.6% vs 3.5%, P = 0.46). The 1-year and 2-year cumulative rates of appropriate ICD therapies were 31.4% and 38.4% for men and 32.6% and 40.8% for women, respectively (P = 0.63). The unadjusted 1-year and 2-year cumulative survival rates were 95.6% and 93.7% for men and 95.7% and 94.3% for women, respectively (P = 0.98). Adjusted total (P = 0.61), sudden (P = 0.82), and cardiac (P = 0.34) death-free survivals also were similar in men and women. CONCLUSION: Despite clinical differences suggesting women are at lower risk than men, men and women with VT/VF who are treated with an ICD have similar arrhythmic event and survival rates. These factors should be considered when determining risk and prescription of ICD therapy for women.