Article, Cardiology

Hemodynamic profiles of ED patients with acute decompensated heart failure and their association with treatment

a b s t r a c t

Background: The hemodynamic profile of patients presenting to the emergency department (ED) with Acutely decompensated heart failure (ADHF) provides the basis for initial management. We characterized the hemodynamic profiles of patients presenting to the ED with ADHF and their association with treatments and outcomes.

Methods: We conducted a retrospective analysis of the National Hospital Ambulatory Medical Care Survey (2006-2010) including ED subjects presenting with ADHF. Patients were classified into 3 groups based on their presenting systolic blood pressure (SBP): hypertensive (HTN) (SBP, >=160), normotensive (NT) (SBP, 100-159), or hypotensive (HYPO) (SBP, b 100). univariate and multivariate analyses were used to determine associations between age, sex, race, and medications administered vs hemodynamic profiles using ?2 test and logistic regression.

Results: There were an estimated 3.4 million ED patient visits for ADHF. Mean age was 69 years, 51% were men, and 65% were white. Hemodynamic profiles at presentation were HTN (32%), NT (48%), and HYPO (21%). Age, sex, and ethnicity were similar across hemodynamic profiles. Rates of admission (HTN [78%], NT [75%], and HYPO [72%]; P = .39) and ED mortality (HYPO, 0.8%; HTN and HYPO, 0% each; P = .12) were not associated with hemodynamic group. Although administration of Loop diuretics was similar across groups (approximately 60%-70% each), vasodilator use (mostly nitroglycerin) was greatest in the HTN group (42%, HTN; 23%, NT; 12%, HYPO; P b .001).

Conclusions: Of HTN ADHF patients, less than half received vasodilators, and approximately one-third did not receive diuretics, in the ED. The development of stratified protocols for therapy based on these profiles should be considered.

(C) 2014

Introduction

The acute management of decompensated heart failure (ADHF) patients in the emergency department (ED) is critical for a multi- tude of morbidity and mortality outcomes, therapeutic interventions, and all-encompassing economic concerns. A 2010 report from the American Heart Association estimated 5.8 million people with heart failure (HF) in the United States in 2006, accounting for 5% of acute hospital admissions and nearly 21 billion dollars in both direct and indirect cost and projected to exceed 160 billion annually by 2030 [1]. Ten percent of all hospitalized patients have HF, and subsequent 1-year mortality rates dramatically rise for each increase in read- mission for HF, from 34% (with 1 readmission) to more than 60% (after the fourth readmission) [2].

? Disclosures: None of the authors have any conflicts of interest.

* Corresponding author. Department of Emergency Medicine, Stony Brook University, Stony Brook, NY 11794-8300, USA. Tel.: +1 631 689 3870; fax: +1 631 444 9719.

E-mail address: [email protected] (A.J. Singer).

Recent guidelines on the management of patients with Acute HF emphasize the importance of the patients’ hemodynamic profile at presentation for both risk stratification and management options [3,4]. The current study was designed to determine the relative fre- quency of the 3 distinct hemodynamic profiles in patients present- ing to US EDs with acute HF and their association with therapeutic

interventions in the acute care environment.

Methods

Study design

We conducted a retrospective analysis of previously collected survey data. The study was exempt from institutional review board because the data are available for public access.

Patients and source of data

The National Hospital Ambulatory Medical Care Survey is part of the ambulatory component of the National Health Care

0735-6757/$ – see front matter (C) 2014 http://dx.doi.org/10.1016/j.ajem.2013.12.005

A.J. Singer et al. / American Journal of Emergency Medicine 32 (2014) 302305 303

Survey that measures Health care use across various types of pro- viders and was inaugurated in 1992 to gather and disseminate information about the health care provided by hospital EDs to the population of the United States. This national probability sample survey, conducted by the Division of Health Care Statistics of the National Center for Health Statistics, Centers for Disease Control and Prevention, samples the target universe of in-person visits made in the United States to EDs of nonfederal hospitals. The sampling frame consists of hospitals listed in the April 1991 Specialty medical group Hospital Database. Hospital weights are applied to make national estimates. Each sampled hospital provides records for a randomly assigned 4-week reporting period. Data abstraction was performed by local hospital staff that was trained by experts from the US Census Bureau using a standardized abstraction form. The abstrac- tors examined all documents in the medical record, including triage sheets, physician history and physical examination results, nursing records, and physician orders. The abstracted data could include up to 3 possible patient reasons for the visit, 3 physician diagnoses, and cause or causes of injury as well as a list of all procedures performed and medications ordered or continued while in the ED. For the study, HF cases were identified using the physician primary diag- noses. The NHAMCS uses the International Classification of Diseases, Ninth Revision, Clinical Modification, to code the diagnoses. An HF case for this study was defined as any physician diagnosis citing codes ICD-9 428.xx of the International Classification of Diseases, Ninth Revision, Clinical Modification, 2.3.

The NHAMCS databases for the years 2006 to 2010 were down-

loaded from the National Center for Health Statistics Web site. Data collected included patient demographics; mode of arrival; time, day, and month of arrival; insurance status; initial vital signs; medi- cation prescriptions; and practitioner type. To calculate Incidence rates of HF, we obtained estimates of the population from the US Census Bureau.

Measures and outcomes

The primary outcome was the use of any diuretic or vasodilator. Secondary outcomes were procedures, admission rates, and mortality during the ED visit.

Data analysis

The data were imported into SPSS 21.0 for Windows (SPSS, Chicago, IL) for analysis. Data elements examined included demo- graphic information, initial vital signs, provider information, insur- ance status, procedures performed, medications prescribed while in the ED, and follow-up information. National estimates were obtained using the assigned NHAMCS patient visit weights.

Patients were classified into 3 hemodynamic groups based on their presenting systolic blood pressure (SBP): normotensive (NT) (SBP, 100-159), hypertensive (HTN) (SBP, >=160), or hypotensive (HYPO) (SBP, b 100). An SBP cutoff of 160 mm Hg was chosen because we believed that some physicians might be less likely to administer intravenous vasodilators to patients with lower blood pressures. Descriptive statistics were calculated, and group compar- isons were performed using univariate (?2 test and analysis of variance) and multivariate (logistic regression for binary data or linear regression for continuous data). Univariate and multivariate analyses were used to determine associations between age, sex, race, and medications prescribed, vs hemodynamic profiles using ?2 test and logistic regression.

Results

There were 921 sample cases in the database over the 6-year study period. A total of 891 (96.7%) contained SBP information and were included in the analyses below. These cases represent an estimated

3.4 million ED patient visits for ADHF from 2006 to 2010. During the same period, the annual number of ED visits rose from 100 to 130 million visits. Although the number of ED visits with a primary diagnosis of ADHF rose over the study period, the rise in ADHF visits paralleled the rise in overall visits.

Mean age was 69 years (95% confidence interval [CI], 69-71 years) (Table 1). Fifty-one percent were men. Sixty-five percent were non- Hispanic whites; 26%, non-Hispanic black; and 7%, Hispanic. Sixty- four percent had Medicare as their primary insurance. Of all patients, 48% had an SBP of 100 to 160 mm Hg, 32% had an SBP greater than 160 mm Hg, and 21% had an SBP of less than 100 mm Hg (Table 1). There were more HTN women (56% vs 44%) but more HYPO men (72

Table 1

Baseline characteristics

SBP b100 (21%)

SBP 100-160 (48%)

SBP N 160 (32%)

P

Mean age (y) (95% CI)

70.5 (68.8-72.2)

69.6 (68.2-70.9)

71.4 (69.4-73.3)

.28

Sex

Female

41

48

56

.04

Male

Race/ethnicity

59

52

43

.09

White, non-Hispanics

62

71

57

Black, non-Hispanics

22

38

40

Hispanic

9

6

8

Other geographic region

Northeast

3

18

2

23

2

21

.88

Midwest

27

24

30

South

35

35

34

West

metropolitan statistical area MSA

20

91

18

82

16

89

.06

Non-MSA

Hospital ownership Nonprofit

9

79

18

83

11

81

.49

Government (nonfederal)

17

9

12

Proprietary

4

8

6

Intubated

0.4

0.1

0.5

.40

Admitted

72

75

78

.48

At least 1 cardiovascular agent

23

34

52

b.001

304 A.J. Singer et al. / American Journal of Emergency Medicine 32 (2014) 302305

Table 2

Percent cases prescribed cardiovascular drugs by category and by blood pressure group

Drug category

All

SBP

b 100

SBP

100-160

SBP

N 160

P

Diuretics Loop diuretic

70%

63%

71%

69%

.53

Potassium-sparing diuretics

1%

0

2

0

.17

Thiazide diuretics

1%

1%

1%

2

.89

Carbonic anhydrase inhibitors

.1%

0

.2%

0

.78

Vasodilators

Nitroglycerin

26%

6%

22%

39%

b.001

Angiotensin-converting enzyme

6%

2%

4%

9%

.007

inhibitors

Calcium-channel blockers

5%

0

6%

5%

.53

Antianginal agents

26%

6

22

39

b.001

Noncardioselective ?-blockers

4%

3%

5%

4%

.677

Antiandrenergic agents

3%

0

.1%

8%

b.001

(centrally acting)

Intropic agents

3%

6%

4%

1%

.06

Anti-HTN combinations

.3%

0

0

.9%

.25

Antiarrhythmics group I

.1%

0

.2%

0

.77

Antiarrhythmics group II

.3%

0

.4%

0

.68

Antiarrhythmics group III

.6%

0

.7%

.6%

.91

Antiarrhythmics group IV

3%

0

4%

1%

.09

Antiarrhythmics group V

2%

0

2%

.4%

.24

vs. 29%). Age, sex, and ethnicity were similar across hemodynamic profiles. The rates of admission were similar across groups (78% of HTN, 75% of NT, and 72% of HYPO patients; P = .48). Endotracheal intubation was similar across groups (Table 1). Emergency depart- ment mortality did not differ by hemodynamic profile (0.8% in NT patients and none in either of the other groups; P = .12).

Cardiovascular medication usage, based on hemodynamic profile, is presented in Table 2. At least 1 cardiovascular medication was prescribed in the ED in 81% of HTN patients, 78% of NT patients, and 68% of HYPO patients (P = .32). Although prescription of loop diuretics was similar across groups (Table 2), vasodilator use (mostly nitroglycerin) was greatest for HTN patients (42% in HTN patients, 23% in NT patients, and 12% in HYPO patients; P b .001).

Discussion

Differentiation of patients with ADHF based on their hemody- namic profile is important because the underlying pathogenesis and requirED treatments may differ [5]. Our results, based on a large nationally representative database, confirm that the number of ED visits for acute HF continued its rise during the period from 2006 to 2010. The rise in number of ED visits for ADHF closely parallels the rise in general ED visits during the study period, whereas the Hospital admission rates remain fairly stable at around 80%. Of all these patients, roughly one-third presented with hypertension; one-half, with normotension; and one-fifth were HYPO.

Support for HTN patients representing a unique physiologic presentation, requiring specific treatment has been published by others. Fonarow et al [6] retrospectively determined that SBP serves as 1 of 3 cornerstones to predict subsequent in-patient mortality, and Gheorghiade et al [7] further suggested that HTN blood pressures confer some form of survival advantage in these patients. In addition, some programs have initiated a triage risk assessment, the Emergency Heart Failure Mortality Risk Grade, which uses SBP in its risk paradigm [8]. Based on the initial SBP, patients presenting to the ED with ADHF can be classified as HTN (SBP, N 160 mm Hg), NT (100-160 mm Hg), or HYPO (b 100 mm Hg). This classification may have important implications with respect to the physiology and management of patients with HF decompensation. Although the gradual (eg, over several days) volume overload of NT HF is usually responsive to diuretics alone, HTN HF deterioration may be sudden and acute, with symptoms rapidly worsening in just a few

hours, due to an increase in systemic peripheral resistance and redistribution of fluid from the central to the pulmonary circulation [5,7]. These patients may benefit from the concomitant use of vasodilators for both preload and afterload reduction. Finally, HYPO HF patients comprise the highest risk patients presenting with ADHF, often times requiring intensive and urgent intervention to forestall further decompensation and its associated increased morbidity, lengthened hospitalization, and mortality.

Given the differing pathogenic mechanisms associated with each presentation, it would be reasonable to assume that HTN patients should be more often treated with vasodilators, whereas NT patients may require diuretics only. Although there is mounting evidence that early initiation of intravenous vasodilators and diuretics in the ED, in appropriate patients, improves outcomes with acute HF [9,10], current guidelines do not specifically tailor therapy based on hemodynamic presentations [3,4]. That there may be benefits from early vasodilator use in HTN patients is supported by several ran- domized controlled trials. The blood pressure control in acute heart failure trial [11], enrolling markedly dyspneic ED ADHF patients presenting with an SBP greater than 140 mm Hg, demonstrated nearly complete resolution of dyspnea associated with lowering the SBP. Using the acute decompensated heart failure (ADHERE) Registry, Peacock et al [9] demonstrated that in-hospital mortality was significantly lower in the group of patients who received vasoactive drugs early in their hospital course (odds ratio, 0.87; 95% CI, 0.79-0.96; P = .006), and the adjusted odds of death increased 6.8% for every 6 hours of treatment delay (95% CI, 4.2-9.6; P b

.0001). Peacock et al also reported that rapid blood pressure

lowering was associated with nearly complete resolution, in as little as 3 hours, with the pure arteriovasodilator clevidipine [11]. In another prospective evaluation of acute dyspnea in ED patients with pulmonary edema treated with nitroglycerin, investigators demon- strated lower endotracheal Intubation rates and intensive care unit admissions [12]. Moreover, in the recently presented phosphodies- terase-5 inhibition to improve quality of life and excercise capacity in Diastolic heart failure study, a 6-month mortality benefit for those receiving relaxin within 8 hours of presentation in addition to standard optimal medical care was demonstrated in 1161 patients presenting with a blood pressure greater than 125 mm Hg [13]. Indeed, many current research trials concerning vasoactive sub- stances for the treatment of ADHF are focused on a minimum SBP for study entry. The results of these studies, in conjunction with our own, suggest that there are a relatively large number of HTN HF patients noted in our analysis who did not receive vasodilators who may potentially benefit from this therapy.

Although our investigation is one of the few to report on ED therapy, similar investigations have been published from inpatient registry data. The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry found that half of all hospitalized patients had an SBP greater than 140 mm Hg, and a fourth had an SBP greater than 160 mm Hg [7]. They also noted that low SBP in their cohort was an independent predictor of morbidity and mortality in patients with HF at hospital admission. Likewise, multivariate analysis identified relative hypo- tension as 1 of 3 risk factors for higher mortality during a hospitaliza- tion for ADHF. The combination of renal dysfunction and an SBP less than 115 mm Hg at the time of hospitalization was associated with acute mortality rates exceeding 20%.

Our analysis also found that as many as one-third of HF patients did not receive diuretics in the ED. This too may represent an opportunity for improved outcomes. Maisel et al [14], in a 15000-patient analysis of the ADHERE registry, reported that as little as a 1-hour delay to diuretic administration is associated with increased short-term mortality in patients with significantly elevated B-type natriuretic peptide. Although we were not able to control for B-type natriuretic peptide levels in our analysis, patients admitted

A.J. Singer et al. / American Journal of Emergency Medicine 32 (2014) 302305 305

with congestive findings (ergo their admission diagnosis) are likely candidates for diuretics in the setting of Elevated blood pressure.

Although we did not control for diuretic dosing, some acknowl- edgement regarding the controversy regarding what is the appropriate dose should be considered and may explain why some patients did not receive any diuretic despite being apparent candidates. Although a 300- patient randomized controlled diuretic optimization strategies evalu- ation study found that diuresis improved, with transiently worsening renal function, if mean (SD) doses of loop diuretic were as high as 131

(51) mg every 12 hours, it is not clear that higher doses than this are safe [15]. An ADHERE registry analysis examining the impact of diuretic dosing found that 62866 patients receiving less than 160 mg vs 19674 patients treated with more than 160 mg had a lower risk for in-hospital mortality, Intensive care unit stay, Prolonged hospitalization, or adverse renal effects [10]. This suggests that although lower doses are safe and effective, the indiscriminate use of high doses of diuretics may not be safe.

Limitations

The major limitation of this study is the retrospective analysis of a prospectively collected data set that renders our conclusions as “hypothesis generating” and cannot determine the causality of in- tervention. However, the NHAMCS is a highly recognized and repre- sentative federally sponsored survey that lends access to a highly divergent patient population. A second limitation is our decision to include patients who were assigned by physicians a diagnosis of ADHF as their primary diagnoses. Thus, we did not include patients who may have had multiple other medical problems that also had coexistent ADHF. In this light, the agreement between the ED physicians’ and discharge diagnoses may have been limited. In some studies, this error rate may be as high as 18.5%. Despite the fact that the estimated total numbers of patients in the NHAMCS database is very large, data analysis is limited to 891 actual patients included in the cohort over a 5-year study limiting the power to draw con- clusions. Furthermore, the NHAMCS does not define the etiology of a patient’s HF deterioration. Finally, we only examined the initial vital signs at the time of patient triage. Because vital signs change over time, we cannot verify that assignment of hemodynamic profiles would be the same later in a patient’s presentation. In addition, our choice of defining HTN HF may be criticized. However, there are little physiologic definitional data to support these cut points, and we felt most would accept the necessity of intervention with symp- tomatic HF and blood pressure greater than 160 mm Hg, whereas SBP less than 160 mmHg would have engendered less consensus for the necessity of treatment. Finally, echocardiographic findings would have been helpful in interpreting our data.

Conclusions

Hemodynamic profiles assist in the initial management decision for patients with ADHF in the ED and have significant ramifications for subsequent morbidity, mortality, and economic outcomes. Because less than half of HTN patients receive any vasodilator and up to a third receive no diuretic while in the ED, the development of stratified protocols for therapy based on these profiles should be considered.

References

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