Adrian Hernandez

Duke University Medical Center | DUMC · Duke Clinical Research Institute

Background New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic “Aspirin Dosing: A Patient-Centric...

Objectives There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge. Methods Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded...

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real‐world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who...

Importance Adoption of guideline-directed medical therapy for patients with heart failure is variable. Interventions to improve guideline-directed medical therapy have failed to consistently achieve target metrics, and limited data exist to inform efforts to improve heart failure quality of care. Objective To evaluate the effect of a hospital and...

Importance Randomized clinical trials (RCTs) are critical in advancing patient care, yet conducting such large-scale trials requires tremendous resources and coordination. Clinical site start-up performance metrics can provide insight into opportunities for improved trial efficiency but have not been well described. Objective To measure the start-...

Background The electronic health record (EHR) contains a wealth of clinical data that may be used to streamline the identification of potential clinical trial participants. However, there is little empirical information on site-level facilitators of and barriers to optimal use of EHR systems with respect to trial recruitment. Methods We conducted...

Aims: We evaluated the relation between baseline and new-onset atrial fibrillation (AF) and outcomes, and assessed whether vericiguat modified the likelihood of new-onset AF in patients with worsening heart failure (HF) with reduced ejection fraction in VICTORIA. Methods and results: Of 5050 patients randomized, 5010 with recorded AF status at b...

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Audio Interview Interview with Dr. J. Michael McGinnis on supporting the evolution of a learning health system. (19:56)Download To help address important health issues, embedded pragmatic clinical trials could generate real-world evidence without the limitations associated with observational studies or the time, expense, and lack of generalizabilit...

Aims Associations between growth differentiation factor-15 (GDF-15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the ‘Functional Impact of GLP-1 for Heart Failure Treatment’ (FIGHT) stud...

Aims Implantable device-based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID-19 (Cov-19) and how these compared with those presenting with decompensated HF or pneumonia. Methods...

Background: Prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VICTORIA trial included high-risk patients with HF and reduced ejection fraction and a recent worsening HF event. The study participants had an unusually high event rate despite...

Background: Sodium glucose co-transporter type 2 (SGLT2) inhibitors, originally developed as glucose lowering agents, have been shown to reduce heart failure hospitalizations in patients with type 2 diabetes without established heart failure, and in patients with heart failure with and without diabetes. Their role in patients with heart failure wi...

Aims Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73m². We evaluated the relationship between the efficacy of vericiguat and b...

Background The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. Methods Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardio...

Aims: Improving the health status (symptoms, function, and quality of life) of patients with heart failure with reduced ejection fraction (HFrEF) is a primary treatment goal. Angiotensin receptor neprilysin inhibitors (ARNI) improve short-term health status in clinical practice, but the sustainability of these improvements is unknown. Methods and...

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence (RWE) in the evaluation of new treatments or products. RWE studies often rely on real-world data (RWD), including data extracted from healthcare records or data captured by mobile phones or...

Coronary artery disease (CAD) is highly prevalent in patients with heart failure (HF) and accounts for nearly two-thirds of cases. The use of percutaneous coronary intervention (PCI) in HF patients with CAD has markedly increased and has been suggested to be associated with improved outcomes in numerous observational studies. Randomized data compar...

Background Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous ferric carboxymaltose leads to early and sustained improvement in patient-reported outcomes and functional capacity in patients with...

Background : Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies. Methods : This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy i...

Volume recruitment from the splanchnic compartment is an important physiological response to stressors such as physical activity and blood loss. In the setting of heart failure (HF), excess fluid redistribution from this compartment leads to increased cardiac filling pressures with limitation in exercise capacity. Recent evidence suggests that bloc...

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real‐world evidence (RWE) in the evaluation of new treatments or products. Real‐world clinical trials or pragmatic trials often differ from traditional clinical trials in the use of open‐label or nonblinded tr...

The randomized controlled trial (RCT) is the gold standard for evaluating the causal effects of medications. Limitations of RCTs have led to increasing interst in using real‐world evidence (RWE) to augment RCT evidence and inform decision‐making on medications. Although RWE can be either randomized or nonrandomized, nonrandomized RWE can capitalize...

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real‐world evidence (RWE) in the evaluation of new treatments or products. The RWE label has been used to refer to a variety of departures from the methods of traditional randomized controlled trials. Recogniz...

Cardiovascular (CV) outcome studies of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shifted the paradigm of type 2 diabetes management given their benefits regarding a reduction in major adverse CV events. However, the relationship between GLP-1 RAs and coronary revascularization remains poorly understood. In this EXSCEL post-hoc anal...

Background Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prognostic value versus a marker of higher risk chronic HF patients is unclear. Methods After excluding patients with new-onset HF, th...

Sharing clinical trial data can provide value to research participants and communities by accelerating the development of new knowledge and therapies as investigators merge data sets to conduct new analyses, reproduce published findings to raise standards for original research, and learn from the work of others to generate new research questions. N...

Importance It is unclear how New York Heart Association (NYHA) functional class compares with patient-reported outcomes among patients with heart failure (HF) in contemporary US clinical practice. Objective To characterize longitudinal changes and concordance between NYHA class and the Kansas City Cardiomyopathy Questionnaire Overall Summary Score...

Background The HERO registry was established to support research on the impact of the COVID-19 pandemic on US healthcare workers.Objective Describe the COVID-19 pandemic experiences of and effects on individuals participating in the HERO registry.DesignCross-sectional, self-administered registry enrollment survey conducted from April 10 to July 31,...

Aims Although models exist to predict amputation among people with type 2 diabetes with foot ulceration or infection, we aimed to develop a prediction model for a broader range of major adverse limb events (MALE)—including gangrene, revascularization, and amputation—among individuals with type 2 diabetes. Methods In a post‐hoc analysis of data fro...

Introduction. Early COVID-19 vaccine acceptance rates suggest that up to one-third of HCWs may be vaccine-hesitant. However, it is unclear whether hesitancy among HCWs has improved with time and if there are temporal changes whether these differ by healthcare worker role. Methods. In October 2020, a brief survey was sent to all participants in the...

Objectives The goal of this study was to evaluate differences in clinical and patient-reported outcomes between women and men hospitalized for acute HF. Background Among patients hospitalized for heart failure (HF), it is unclear if symptom burden, response to therapy, and patient-reported quality of life (QOL) are different in women as compared w...

Objectives The authors estimated changes of stressed blood volume (SBV) induced by splanchnic nerve block (SNB) in patients with either decompensated or ambulatory heart failure with reduced ejection fraction (HFrEF). Background The splanchnic vascular capacity is a major determinant of the SBV, which in turn determines cardiac filling pressures a...

Background and purpose Depression is common after stroke and is often treated with antidepressant medications (AD). ADs have also been hypothesised to improve stroke recovery, although recent randomised trials were neutral. We investigated the patterns of in-hospital AD initiation after ischaemic stroke and association with clinical and readmission...

Aim : The inflammatory cytokine interleukin-6 (IL-6) has been previously implicated in the pathophysiology of acute decompensated heart failure (HF). Prior observations in acute HF patients have suggested that IL-6 may be associated with outcomes and modulated by nesiritide. We aimed to evaluate the associations between serial IL-6 measurements, mo...

Background In patients with heart failure and reduced ejection fraction (HFrEF), angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists (MRA), and beta-blocker (βB) are underutilized. It is unknown if patients with and witho...

Aims: Metformin, the most common first-line therapy for type 2 diabetes, is used frequently in patients with moderate and severe chronic kidney disease (CKD), despite concerns regarding lactic acidosis. We aim to provide evidence on the cardiovascular and renal safety of metformin in CKD3-4. Materials and methods: This posthoc analysis compared...

Objective To describe PCORnet, a clinical research network developed for patient-centered outcomes research on a national scale. Study Design and Setting Descriptive study of the current state and future directions for PCORnet. We conducted cross-sectional analyses of the health systems and patient populations of the 9 Clinical Research Networks a...

Background Ultrafiltration is not commonly used because of higher incidence of worsening renal function without improved decongestion. We examined differential outcomes of high versus low fluid removal and preserved versus reduced ejection fraction (EF) in CARRESS‐HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Methods and Resu...

Aims: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition, and tissue congestion manifested by oedema is not present in all patients. We compared clinical characteristics, exercise capacity, and outcomes in patients with HFpEF with and without oedema. Methods and results: This study was a post hoc analysis of pool...

Importance Influenza is temporally associated with cardiopulmonary morbidity and mortality among those with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher influenza vaccine dose has been associated with reduced risk of influenza illness. Objective To evaluate whether high-dose trivalent influenza vaccin...

Background In VICTORIA, vericiguat was more effective than placebo in addition to standard of care in reducing the composite outcome of CV death (CVD) or HF hospitalization (HFH). We describe baseline guideline-directed medical therapy (GDMT) and examine if the primary outcome was associated with differences in adherence to GDMT including dosing....

Objectives The authors sought to evaluate the association of heart failure hospitalization (HFH) with guideline-directed medical therapy (GDMT) prescribing patterns among patients with heart failure with reduced ejection fraction (HFrEF). Background HFH represents an important opportunity to titrate GDMT among patients with HFrEF. Methods The CHA...

Introduction: The importance of self-care behaviors in successful heart failure (HF) management is widely recognized. And yet, patient perspectives on strategies to effective carry out the work of behavior change remain relatively unexplored. Methods: From March 2017 to May 2017, we conducted semi-structured, in-depth interviews with 8 HF patients...

Introduction: How the New York Heart Association classification system compares with patient-reported outcomes for HF patients in contemporary U.S. clinical practice is unclear. Methods: Among 2,872 U.S. outpatients with chronic HF with reduced ejection fraction (HFrEF) in the CHAMP-HF registry with complete NYHA class and Kansas City Cardiomyopath...

Introduction: The VICTORIA (Vericiguat Global Study in Subjects with HF with Reduced EF) trial included 5050 patients in 3 discrete subgroups reflecting their index worsening heart failure (HF) event: <3 months after HF hospitalization (HFH) (n=3366), 3-6 months after HFH (n=871), and those requiring IV diuretic therapy without HFH within the prior...

Importance The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH. Objective To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With He...

Objectives The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization. Background Vericiguat compared with placebo reduced the primary outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH) in patients with HF with re...

Importance Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life. Objective To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Qu...

Background: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial. Methods and results: T...

Background: In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) vs. enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice. Methods: PROVIDE-HF was a prospective study within a national research network (PCOR...

With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended gl...

Cluster randomized trials (CRTs) refer to experiments with randomization carried out at the cluster or the group level. While numerous statistical methods have been developed for the design and analysis of CRTs, most of the existing methods focused on testing the overall treatment effect across the population characteristics, with few discussions o...

The editors of JAMA Cardiology place an editorial priority on the valuation of medical advances in addition to the evidence base supporting a medical or device therapy. This is critical to determine the appropriate value-based price benchmarking and priority of novel therapeutics, especially when multiple therapies may increase the risk of financia...

Background: National data from diverse institutions across the United States are critical for guiding policymakers as well as clinical and public health leaders. This study characterized a large national cohort of patients diagnosed with COVID-19 in the U.S., compared to patients diagnosed with viral pneumonia and influenza. Methods and Findings: W...

Patients hospitalized for heart failure (HF) remain at high risk for early readmission. A post hoc analysis was performed of the biomarker substudy of the ASCEND-HF trial. An in-hospital congestion score was derived using orthopnea, pedal edema, and NT-proBNP levels. Its added prognostic value beyond traditional risk factors was assessed by determi...

Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making...

Objective To describe the intent and early outcomes of elective inotrope use during heart failure hospitalization. Patients and Methods A prospective multisite design was used to collect data for hemodynamically stable patients started electively on inotrope therapy between January 1 and August 31, 2018. We prospectively recorded data when intrave...

Amid the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, substantial effort is being directed toward mining databases and publishing case series and reports that may provide insights into the epidemiology and clinical management of coronavirus disease 2019 (COVID-19). However, there is growing concern about whether attempts t...

UNSTRUCTURED Sharing clinical trial data can provide value to research participants and communities by accelerating the development of new knowledge and therapies as investigators merge data sets to conduct new analyses, reproduce published findings to raise standards for original research, and learn from the work of others to generate new research...

Every year, hospitals are ranked or rated by public and private organizations that aim to identify centers that provide high-quality health care. Although the reports are intended to help guide consumers in determining where to seek care, these ranking systems often yield conflicting information or, worse, misinformation for patients and their clin...

Background Among patients with heart failure (HF) with reduced ejection fraction (EF), improvements in left ventricular EF (LVEF) are associated with better outcomes and remain an important treatment goal. Patient factors associated with LVEF improvement in routine clinical practice have not been clearly defined. Methods CHAMP-HF (Change the Manag...

In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to infor...

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infectio...

Objectives We hypothesized that splanchnic nerve blockade (SNB) would attenuate increased exercise-induced cardiac filling pressures in patients with chronic HF. Background Chronic heart failure (HF) is characterized by limited exercise capacity driven in part by an excessive elevation of cardiac filling pressures. Methods This is a prospective,...

The PARADIGM-HF trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in PARADIGM-HF had NYHA class IV symptomology; accordingly, data that informs...

Background The FIGHT (Functional Impact of GLP-1 [glucagon-like peptide-1] for Heart Failure Treatment) trial randomized 300 patients with heart failure with reduced ejection fraction (HFrEF) and a recent hospitalization for heart failure to liraglutide versus placebo. While there was no difference in the primary outcome (rank score of time to deat...

Objectives The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies. Background Specifi...

BACKGROUND Little is known about the impact of accountable care organizations (ACO) on hospitalized heart failure (HF) patients, a high-cost and high-risk population. OBJECTIVE We linked Medicare fee-for-service claims from 2013 to 2015 with data from American Heart Association Get With The Guidelines –HF registry to compare HF care, post-discharg...

Pragmatic clinical trials involving random treatment assignment embedded in everyday practice aim to efficiently generate relevant and valid evidence regarding real-world treatment decisions. Such trials often face barriers, but steps can be taken to facilitate them.

Background: Current guidelines recommend evaluation for underlying heart disease and reversible conditions for patients with new-onset heart failure (HF). There are limited data on contemporary testing for coronary artery disease (CAD) in patients with new-onset HF. Methods: We performed an observational cohort study using the Get With The Guide...

Background In PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-pro BNP in Patients Stabilized From an Acute Heart Failure Episode), the in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure (ADHF) was well-tolerated and led to improved outcomes. We aim to determi...

Lipoprotein (a) [Lp(a)] is a low-density, cholesterol-containing lipoprotein that differs from other low-density lipoproteins due to the presence of apolipoprotein(a) bound to its surface apolipoprotein B100. Multiple epidemiologic studies, including Mendelian Randomization studies, have demonstrated that increasing Lp(a) levels are associated with...

Background The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. Methods In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with...

Importance Little is known about the utilization rates and outcomes of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) placement among patients with advanced heart failure (HF). Objective To examine utilization rates, patient characteristics, and outcomes of ICD and CRT-D placements among pa...

Importance Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question. Objective To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD...

This joint Canadian Heart Failure Society (CHFS) and the CCS Heart Failure guidelines report has been developed to provide a pan-Canadian snapshot of the current state of clinic-based ambulatory heart failure (HF) care in Canada with specific reference to elements and processes of care associated with quality and high performing health systems. It...

The TOPCAT trial investigated spironolactone vs placebo in patients with HFpEF. While the primary endpoint was not statistically significant, treatment with spironolactone did reduce heart failure hospitalizations compared with placebo. TOPCAT's impact on prescribing patterns in the U.S. is not well-characterized. We performed a retrospective analy...