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Weintraub et al

Acute Heart Failure Syndromes


ume status by assessing measurements and changes in size of the inferior vena cava.184 –187 Although not included in any of the criterion-based standards, echocardiographic parameters of systolic and diastolic dysfunction may be, in the proper clinical context, highly suggestive of AHFS. Echocardiogram findings clearly contribute to the criterion standard diagnosis in AHFS diagnostic trials. Further, HF with preserved systolic function (HFPSF) is prevalent, accounting for approximately 50% of hospital admissions for AHFS. In-hospital mortality rates appear to be slightly lower (3% in OPTIMIZE-HF and 2.8% in ADHERE) when compared with rates in patients with left ventricular systolic dysfunction. Length of stay and rates of readmission are similar.11,188 It will be important to enroll and further characterize patients with AHFS and HFPSF to improve the evidence base that influences clinical care.

Despite its clear utility in AHFS, access to formal echo- cardiography performed in the ED outside of weekday daytime hours is rare. Reasons may vary, but most hospitals across the country simply do not have the available resources and personnel. Over the past decade, however, there has been rapid expansion in point-of-care ultrasound expertise among ED providers. Achievement of basic proficiency is now considered a requisite skill for all emergency medicine residency graduates. Accordingly, there is growing interest among ED providers in the potential applicability of limited cardiac ultrasonography in patients with suspected AHFS. Prior studies have shown that, after a brief period of focused training, emergency physicians can competently estimate

ejection fraction189 of mitral inflow,189,190 and accurately perform Doppler analysis thereby permitting rapid definition of

determine its impact on outcomes.199 –200 It is important to note that past clinical trials in AHFS have largely bypassed the ED phase of management, enrolling patients 24 to 48 hours after admission. Depending on the drug’s pharmacody- namic properties, it is possible that a therapeutic window exists beyond which apparent efficacy is diminished. For

dyspnea relief, a key end point in AHFS,83,202

this may be

particularly true. Current therapeutic trials targeting dyspnea relief have significantly shortened the time window of enroll- ment to capture patients when symptoms are most severe—on ED presentation.202,203

Goals of ED Management Although preliminary data suggest that prompt ED intervention impacts outcomes in terms of in-hospital morbidity and mortal- ity,200,201 it is not clear whether this extends to more intermediate-term outcomes, such as 30- to 60-day rehospital- ization, or mortality. After addressing immediate life-threatening conditions, the current approach to ED management moves quickly to a focus on symptomatic improvement, which drives subsequent therapeutic decisions. Intermediate-term goals there- fore become a secondary priority. It is possible, however, that such outcomes could be influenced by ED management, espe- cially if it were to produce either of the following: (1) sufficient interruption of a pathophysiologic process that actively contrib- utes to the acute, decompensated state; or (2) significant un- wanted downstream effects such as renal or myocardial injury. Although existing data regarding these considerations are lim- ited, understanding how acute therapy impacts underlying car- diorenal function and hemodynamic end points is critical to the development of more progressive, outcome-oriented AHFS care.

global cardiac function. This capability would: (a) help direct appropriate intervention to the right patient, (b) delineate structure/function in the heart before the initiation of therapy, and (c) improve understanding of the phenotypes of AHFS.18 If coupled with thoracic ultrasound191 and left atrial volume measurement,192–194 a real-time, noninvasive depiction of lung fluid burden as it relates to underlying cardiac dysfunction and acute left ventricular filling pressure could be obtained. Interpreted within the context of ED blood pressure, which is both a primary manifestation of AHFS etiology186,195–197 and a critical determinant of outcome,12,103 and information de- rived from interrogation of implanted monitoring devices, if present, a phenotype-oriented approach to management may be achievable.60,61

Novel Approaches to Therapy Based on an improved understanding of AHFS pathophysi- ology, lessons learned from largely disappointing clinical trials (Table 2), and the high postdischarge event rate, it is clear that novel approaches and strategies are needed.198 Such strategies should be aligned with appropriate end points that are based on the mechanism of action and goals of the intervention. Furthermore, they should be designed to address the potential time-dependent nature of AHFS management, the importance of which, in contrast to acute coronary syndrome (ACS) care, has not been well explored. Previous retrospective studies suggest that time to treatment may be important in AHFS, but it must be prospectively studied to

Patient Characterization A more complete understanding of patients at the time of presentation and their response to current management is needed to better target future research. Current clinical profiles are largely based on inpatient hospital registries204–206 but these do not include important information on acute cardiac function, which may be available via focused bedside echocardiogram, nor do they provide data on immediate and short-term responses to standard ED therapy. Consequently, the natural history of ED patients hospitalized for AHFS is not well described. We are in need of comprehensive clinical, laboratory, and neurohormonal data from the time of ED presentation through the postdischarge phase. A prospective observational database that includes these parameters, as well as the ability to investigate novel cardiac and renal injury biomarkers, would help address this knowledge gap and add substantially to our current appreciation of AHFS. Results could then be used as a guide to define clinical profiles and guide short-term management (Table 3).4,21 Nitrates, for example, might be used in higher relative doses to diuretics in the hypertensive profile, or ultrafiltration could be used in the

diuretic-resistant patient.207,208

Conversely, inotropic agents

should be considered in the rarer cases of advanced/low- output HF. Several different profiles have been suggested for future subcategorization.5,21 The European Society of Cardi- ology66 suggests that patients can be categorized into 6 possible profiles, with overlap between categories: (1) worsen-

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