Weintraub et al
Acute Heart Failure Syndromes
while they are still in the ED. Some view the ED as too chaotic of an environment to successfully screen, consent, and enroll patients. This is often the reason identified as the primary barrier to conducting clinical trials in the ED.3 However, this has been found to be largely untrue. Careful planning is necessary so that identification and enrollment in the ED is followed by transition of the patient to an inpatient research team that assumes or shares the trial duties with the ED team. An example of this team approach is the Emergency Management and Research Group in Acute Heart Failure (EMERG-HF).3 This model, in general, uses 2 physicians to lead an interdisciplinary team of emergency physicians, cardiologists, research nurses, study coordinators, and research assistants. The emergency medicine team is respon- sible for screening, consenting, and performing randomization, as well as providing the initial care and data collection. Although dependent on bed availability, when the patient is admitted to the hospital, the care and trial responsibilities are transferred to the cardiology team.
Depending on departmental research infrastructure, there are a few different ED methods of screening and enrolling patients. One cost-efficient process of enrollment uses study assistants to perform the initial screening. Once the patient passes initial screening, the study team (nurse and/or physi- cian) is activated to complete the screening process and consent and enroll the patient. Another alternative is to have a research nurse perform both screening and enrollment. This model is usually used when there are multiple research protocols going on simultaneously, allowing the research nurse to screen for more than one trial, and maximizing opportunities for enrollment.
Another issue to consider is a patient’s capacity to provide informed consent, which may impede enrollment depending on the severity of the acute illness. However, these issues are surmountable with proper planning before trial initiation. Over the past decade processes for satisfying regulatory requirements have gone through rigorous review and are now well devel-
In extreme cases, when a patient’s decision
making capacity is expected to be so impaired as to impede the consenting process, exception from informed consent may be necessary. Exception from informed consent requires significant resource allocation to obtain community input regarding the trial, but allows inclusion of patients who otherwise could not be enrolled.
Successful ED enrollment requires a coordinated effort in- volving the physicians, nurses, and study assistants of both emergency medicine and cardiology. Delineation of responsibil- ities and coordination of an on-call schedule for the study team is critical for success. These processes often require several weeks of meetings before trial commencement. However, once the infrastructure is put into place, it can be easily adapted from one trial to the next.
Summary The economic burden of HF and AHFS on the healthcare system continues to increase. The vast majority of patients hospitalized for AHFS present to the ED. As a result, emergency medicine physicians have become the gatekeepers for patients with AHFS. It is clear there are many unanswered questions about the optimal workup, treatment, and disposition of the ED patient
ACS 1 million/y
AHFS 1 million/y
Prehospital In-hospital 60–90 d Targets of therapy Clinical trial results ACC/AHA Guidelines
High 3%–4% 2% Clearly defined-thrombosis Beneficial Level A
? 3%–4% 10% Unclear Minimal, no benefit, harmful Minimal level A/B, mostly C
Table 5. A Comparison of Characteristics, Pathophysiologic Targets of Therapy and Evidence in Management of Patients With ACS and AHFS
with AHFS. Although there have been significant life-sustaining advancements in the outpatient management of chronic HF, with the exception of natriuretic peptide testing, there have been no significant breakthroughs in AHFS care in the past several decades. Despite the profound heterogeneity in AHFS presenta- tions, therapeutic options for patients with AHFS have remained largely unchanged during this time period; AHFS therapy continues to focus on fluid removal with intravenous diuretics. Even though this produces early and sustained improvement in symptoms in the majority of ED patients with AHFS, its downstream impact on renal and myocardial function, hemody- namics, and short-term outcomes has not been rigorously studied in the acute setting.
Several possible reasons exist for the lack of improvement in AHFS care and the disappointing results of clinical trials.3 However, a common link among all of these trials has been a universal paucity of ED enrollment. Although acute therapy and symptomatic improvement occurs in less than 6 hours in the vast majority of patients, patients are typically randomly assigned to therapeutic trials long after this time.83 Initial therapy remains largely unaccounted for in trial design despite its impact on symptoms and its association with untoward events such as renal insufficiency and hypotension.7,89–91 Disease management pro- grams have targeted the high-risk hospitalized patient, but have failed to enroll the ED patient who may be discharged home, where socioeconomic barriers are also prevalent and result in a high 30-day recidivism.230,233
ED patients have not been enrolled in AHFS trials largely because of a misconception about the inability to enroll patients in the ED early in their course of therapy. This view has been found to be largely inaccurate. Emergency physicians have a track record of enrolling complex patients in a variety of therapeutic trials for ACS, major trauma, acute ischemic stroke,
and recently AHFS.72,203,234–236
This critical momentum needs to
continue through partnerships with cardiology, which will en- sure continuity in clinical trial management and improvement in AHFS care as patients transition from the ED through hospital- ization to hospital discharge. These collaborations need to begin at the local level and extend to national and international trial design and conduct.
Our current approach to AHFS is similar to the approach to ACS preceding the understanding of coronary artery pathophysiology (Table 5). Elucidation of the pathophys- iology, in conjunction with ED-based intervention trials of