Acute Heart Failure

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 69, NO. 25, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jacc.2017.04.044

EDITORIAL COMMENT

Acute Heart Failure One Syndrome or Many?* Scott D. Solomon, MD, Akshay S. Desai, MD, MPH

R

ecent updates to clinical guidelines (1,2)

death or hospital readmission and, accordingly,

underscore the considerable progress that

management of acute HF syndromes remains largely

has been made in the development of effec-

empiric and consensus-driven.

tive therapy for ambulatory patients with chronic HF

A central challenge in the design of effective

(HF) and reduced ejection fraction. The expanding

clinical trials for acute HF is that there is no generally

arsenal of therapies proven to reduce morbidity and

agreed

mortality in chronic HF and reduced ejection fraction

hospitalization. Accordingly, patients with diverse

has only served to underscore the lack of effective

pathophysiology and risk for adverse outcomes are

treatments for patients with HF and “preserved” ejec-

typically grouped as a single entity, with the pre-

taxonomy

for

HF

syndromes

requiring

tion fraction and those with acute decompensated HF.

dictable result that any signal of treatment benefit is

Irrespective of ejection fraction, hospitalization for

diluted by the noise of disease heterogeneity. In this

acute decompensated HF is recognized as a sentinel

issue of the Journal, Greene et al. (6) present a sec-

event in the life cycle of patients with HF, bringing a

ondary analysis of the ASCEND-HF (Acute Study of

high risk for recurrent hospitalization (nearly 50% at

Clinical Effectiveness of Nesiritide in Decompensated

6 months) and a 1-year risk for mortality of nearly

Heart Failure) trial examining differences in the

30% (3,4). Heart failure is already the leading cause of

clinical characteristics and outcomes of 2 important

hospitalization in the Medicare-eligible population,

subsets of patients with acute decompensated HF:

and the burden of HF admissions is projected to increase over time, with staggering implications for

SEE PAGE 3029

overall health care costs. Recognizing the need to

those with a de novo presentation or recent diagnosis

improve management of acute HF syndrome, treat-

of HF and those with acute worsening of chronic HF

ment guidelines have been published (2,5), but few

of longer duration. Of the 7,141 patients across the

randomized controlled trial data are available to

spectrum of ejection fraction hospitalized with acute

support the recommendations. Most attempts at

decompensated HF and randomized to treatment

pharmacological therapy of acute decompensated

with nesiritide or placebo in ASCEND-HF, the dura-

HF have failed to meaningfully influence rates of

tion of HF before randomization was reported by investigators in 5,741 (80.4%) patients. The 1,536 enrolled subjects for whom HF was reported as

*Editorials published in the Journal of the American College of Cardiology

recently diagnosed (within 30 days of the index HF

reflect the views of the authors and do not necessarily represent the

admission) were more likely to be women with non-

views of JACC or the American College of Cardiology.

ischemic heart disease, higher ejection fraction,

From the Cardiovascular Division, Brigham and Women’s Hospital, Bos-

higher baseline blood pressure, better renal function,

ton, Massachusetts. Dr. Desai has received consulting fees and research

and fewer comorbidities than those with HF of longer

grants from Novartis; and consulting fees from AstraZeneca, Abbott, Relypsa, Janssen, and Sanofi. Dr. Solomon has received research grants

duration. Despite adjustment for these lower risk

from Alnylam, Amgen, AstraZeneca, Bellerophon, Celladon, Gilead,

features, patients with recently diagnosed HF had

GlaxoSmithKline, Ionis Pharmaceutics, Lone Star Heart, Mesoblast,

better prognosis than those with longer duration HF,

MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, Theracos; and is a consultant for Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers

with less dyspnea reported at 24 h and lower rates of

Squibb, Corvia, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis,

mortality at 180 days. Differences between recent-

Pfizer, Takeda, and Theracos.

onset HF and worsening of chronic

HF were

Solomon and Desai

JACC VOL. 69, NO. 25, 2017 JUNE 27, 2017:3040–1

One Syndrome or Many?

consistent in subgroups defined according to age,

those with newly identified disease and that the

race, HF etiology, and ejection fraction. There was a

response to therapy might similarly vary in these

nominal statistical interaction according to sex, sug-

populations. As the authors note, these data com-

gesting a more pronounced association between HF

plement evolving evidence that worsening of chronic

duration and 180-day mortality in women than in

HF may have similar prognostic implications when it

men.

is documented in the ambulatory setting as in

A few caveats are important to note. First, data

situations when it provokes the need for hospital

regarding the duration of HF were derived from

admission (7). The data argue for more careful seg-

unvalidated investigator reports and were unavailable

mentation of the acute HF population at the time of

for nearly 20% of patients (6). Although the patients

trial entry, as well as a more thorough ascertainment

with missing data did not systematically differ from

of worsening HF endpoints, independent of the

those included in the study, it is difficult to exclude

treatment context in which they occur.

residual confounding by selection bias. Second, hos-

Importantly, these data represent only one step

pitalization outcomes were adjudicated only to 30

toward a more granular classification of acute HF

days’ post-discharge, limiting the power to infer dif-

syndromes. Current guidelines postulate that there

ferences in readmission rates according to HF dura-

may be value to further subcategorization of patients

tion. Finally, it remains unclear whether a different

based on hemodynamic profiles at presentation,

threshold for “recent” onset might have altered the

admitting blood pressure, precipitating factors (e.g.,

results. Among those with HF duration >30 days, there

acute coronary syndrome, arrhythmias, valvular dis-

was no clear, graded relationship between HF duration

ease, pulmonary embolism), and clinical features

and clinical outcomes; thus, it would seem that the

(e.g., the presence or absence of pulmonary edema);

most relevant distinction may be between hospitali-

however, none of these designations has been

zation for onset of truly “new” HF (a de novo diag-

systematically used in the design of clinical trials of

nosis) and worsening of established HF.

novel therapeutics in practice. Expanding ambulatory

Despite these limitations, the data of Greene et al.

alternatives to hospitalization for the management of

(6) highlight that the subset of patients who are

patients with HF and worsening congestion mean

newly or recently diagnosed is a potentially distinct

that hospitalization is no longer a sufficient surrogate

and lower risk phenotype of acute HF from the

for identifying patients with worsening HF, whatever

balance of patients with acute exacerbations of

the etiology. Real progress in the effective treatment

chronic or established disease. Intuitively, this the-

of acute decompensated HF may rely on a taxonomy

ory makes sense, because those hospitalized with

that is driven by meaningful pathophysiological

worsening

distinctions and is agnostic to the location in which

HF

represent

patients

with

disease

progression despite application of effective therapy,

care happens to be delivered.

whereas those with new-onset disease may be treatment naive and might be stabilized with appropriate

ADDRESS

medical therapy. The implication is that HF hospi-

Solomon, Cardiovascular Division, Brigham and Women’s

FOR

CORRESPONDENCE:

talization is a more efficient discriminator of risk in

Hospital, 75 Francis Street, Boston, Massachusetts 02115.

patients with an established HF diagnosis than in

E-mail: [email protected].

Dr. Scott D.

REFERENCES 1. Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2016;68:1476–88. 2. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart

Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129–200. 3. Desai AS, Stevenson LW. Rehospitalization for heart failure: predict or prevent? Circulation 2012; 126:501–6. 4. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006;355:251–9. 5. Weintraub NL, Collins SP, Pang PS, et al. Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association. Circulation 2010;122:1975–96.

6. Greene SJ, Hernandez AF, Dunning A, et al. Hospitalization for recently diagnosed versus worsening chronic heart failure: from the ASCEND-HF trial. J Am Coll Cardiol 2017;69: 3029–39. 7. Okumura N, Jhund PS, Gong J, et al. Importance of clinical worsening of heart failure treated in the outpatient setting: evidence from the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure Trial (PARADIGM-HF). Circulation 2016; 133:2254–62.

KEY WORDS acute decompensated heart failure, heart failure, hospitalization, readmission

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