Original Contribution

hypertensive heart failure: patient characteristics, treatment, and outcomes^?

Frank Peacock MD ^a,?, Alpesh Amin MD ^b, Christopher B. Granger MD ^c, Charles V. Pollack Jr MD ^d, Phillip Levy MD ^e, Richard Nowak MD ^f,

Kurt Kleinschmidt MD ^g, Joe Varon MD ^h, Allison Wyman ⁱ, Joel M. Gore MD ⁱ For the Stat Investigators

^aThe Cleveland Clinic, Cleveland, OH, USA

^bUCIMC, Orange, CA, USA

^cDuke Clinical Research Institute, Durham, NC, USA ^dPennsylvania Hospital, Philadelphia, PA, USA ^eWayne State University, Detroit, MI, USA

^fHenry Ford Health System, Detroit, MI, USA

^gUT Southwestern Medical Center, Dallas, TX, USA

^hThe University of Texas Health Science Center, Houston, TX, USA

ⁱCenter for Outcomes Research, UMass Medical School, Worcester, MA, USA

Received 2 February 2010; revised 18 March 2010; accepted 18 March 2010

Abstract

Background: Acute heart failure is a common, poorly characterized manifestation of Hypertensive emergency. We sought to describe characteristics, treatment, and outcomes of patients with severe hypertension complicated by AHF.

Methods and Results: The observational retrospective Studying the Treatment of Acute hypertension (STAT) registry records data on emergency department and hospitalized patients receiving intravenous therapy for Blood pressure greater than 180/110 mm Hg in 25 US hospitals. A subset of patients with HF was defined as pulmonary edema on Chest x-ray or an elevated B-type natriuretic peptide level (BNP N 500 or NTproBNP N 900 pg/mL) in patients with creatinine level 2.5 mg/dL or less. Remaining STAT patients, after excluding those with a primary neurologic diagnosis, constitute the non-HF cohort. An adverse Composite outcome was defined as mechanical ventilation, intensive care unit admission, hospital length of stay more than 1 week, or death within 30 days. Of 1199 patients, 302 (25.2%) had AHF. Acute HF patients and non-AHF patients were similar in age, sex, and overall mortality, but AHF patients were more commonly African American, with a history of HF, diabetes or chronic obstructive pulmonary disease, and prior hypertension admissions. heart failure patients had higher creatinine and natriuretic peptide levels but lower ejection fraction. They were more likely admitted to the ICU; receive electrocardiograms, bilevel positive airway pressure ventilation, and

^? Funding: STAT was supported by a research grant from the Medicines Company(TM).

* Corresponding author. Emergency Services/Desk E-19, Cleveland Clinic, Cleveland, OH 44022, USA. Tel.: +1 216 445 4546; fax: +1 216 445 4552.

E-mail address: [email protected] (F. Peacock).

0735-6757/$ - see front matter (C) 2011 doi:10.1016/j.ajem.2010.03.022

CXRs; and be readmitted within 90 days. Finally, BP decreases lower than 120 mm Hg within 12 hours were associated with an increased rate of the composite adverse outcome.

Conclusions: Acute HF as a manifestation of hypertensive emergency is common, more likely in African Americans, and requires more clinical resources than patients with non-HF-related severe hypertension. Accurate BP control is critical, as declines less than 120 mm Hg were associated with increased Adverse event rates.

(C) 2011

Introduction

Hypertensive crises, consisting of urgencies (without end- organ damage) and emergencies (with end-organ damage), are reported to account for 25% or greater of all emergency department (ED) Medical emergencies [1] and may result in 3% of all ED visits. Overall, approximately 1% of patients who have long-term hypertension will experience a crisis in their lifetime [2]. If untreated, the 1-year mortality of Uncontrolled hypertension is high [3], and in patients presenting with crises, the 5-year Death rate is 26% [4].

Heart failure is a significant public health challenge. It is estimated that there are approximately 1.1 million annual US ED visits for HF [5,6], of which 80% require hospitalization. Once hospitalized, the in-hospital HF mortality rate is 2% to 20% [7,8]. After discharge, 11% die within 30 days, 44% require rehospitalization within 6 months, and 33% do not survive 1 year [7]. As an index event, ED HF presentations are associated with increased short-term mortality risk [9]. If admitted from the ED to the intensive care unit (ICU) for acute HF (AHF), in-hospital mortality exceeds 10% [8]. Finally, an ED presentation for acute pulmonary edema has a particularly poor prognosis; 12% die during their admission and greater than 40% within 1 year [10].

ED investigations report that 53% to 73% of all patients presenting with AHF have a history of hypertension [7,10], with hypertension somewhat more prevalent in preserved (vs reduced) systolic function (76% vs 66%; P b .0001) [11]. More than 60% of patients with AHF have normal or Elevated blood pressure (BP), and some report they have a lower mortality than patients with lower BP [12].

Hypertensive emergencies presenting as AHF have been poorly described. Our purpose was to describe the characteristics, treatment, and outcomes of patients present- ing with severe hypertension complicated by AHF and compare them to the population presenting with severe hypertension without HF.

Methods

The Studying the Treatment of Acute HyperTension (STAT) registry is a US, multicenter, observational, cross- sectional survey of the management practices and outcomes for patients with acute, severe hypertension receiving parenteral Antihypertensive therapy [13]. Its main objectives

included describing outcomes of patients with acute severe hypertension by collecting characteristics of hospitalized patients, exploring practice patterns variation, resource use, and factors leading to Treatment decisions.

A total of 25 hospitals participated in STAT. Sites were selected to include a mix of public and private settings, with broad geographic distribution. Eligible patients were older than 18 years, presenting to the hospital with acute, severe hypertension and receiving treatment in a nonoperative, critical care setting. Severe hypertension was defined as at least one BP documented greater than 180 mm Hg systolic and/or greater than 110 mm Hg diastolic. Patients were excluded if they received hypertension therapy during the peripartum period, had a primary neurologic etiology for their presentation, had therapy delayed longer than 24 hours, and were treated with “comfort care measures” only.

Consecutive patients receiving parenteral antihyperten- sives were retrospectively identified by query of each hospital’s pharmacy database. To be included, patients must have received more than 1 antihypertensive bolus or have received a continuous Antihypertensive infusion within 24 hours of hospitalization.

Reviewers abstracted medical records by standardized case report forms more than 90 days after treatment of hypertension. Data were collected on demographics, hospital investigations, antihypertensive therapies, transition from parenteral to oral dosing, resource use, and outcomes. For medications, the Angiotensin converting enzyme inhibitor /angiotensin receptor blocker (ARB) category includes patients on either an ACEI or an ARB. Patients receiving both were counted only once. Information was also collected about postdischarge events within 90 days. Deaths were tracked for 6 months after hospitalization and validated by the Social Security Death Index.

Acute HF was defined as pulmonary edema on x-ray or elevated B-type natriuretic peptide level (BNP N 500 or NTproBNP N 900 pg/mL) in those with a serum creatinine level 2.5 mg/dL or less. Patients were dichotomized into 2 cohorts based on AHF status.

End-organ damage was defined as hypertension-associ- ated emergencies occurring or worsening during the short- term hospitalization or considered new by the treating physician. This included encephalopathy, any myocardial infarction, unstable angina with dynamic ST changes, renal insufficiency, microangiopathic hemolytic anemia, or aortic dissection. For this analysis, patients presenting with any type of acute stroke or Intracranial bleeding (including

ophthalmologic) were excluded, unless this occurred after hospitalization.

This study was supported by a grant from The Medicines Company to the Center for Outcomes Research (University of Massachusetts Medical School, Worcester, Mass), with the approval of all local institutional review boards, and in compliance with all regulations of participating hospitals.

Data analysis

Descriptive statistics were performed on all patients. Continuous variables are reported as medians with inter- quartile range with categorical variables expressed as proportions. Kruskal-Wallis tests were used to compare medians of continuous data; t tests were used to compare means. ?2 tests were performed for categorical variables. A composite adverse event rate was defined as mechanical ventilation, ICU admission, in-hospital length of stay longer than 7 days, or in-hospital or 30-day death. All analyses were conducted using SAS statistical software (version 9.1) (SAS Institute, Cary, NC).

Results

Overall, there were 1199 STAT registry patients. Their median age was 57 years, 48% were women, and 62% were African American. Most had a prior hypertension (92%), and 33% had a prior hospitalization for hypertension. From this

Table 1 Demographics of AHF vs non-HF STAT patients

cohort, 302 (25.2%) were defined as AHF. Acute HF and non-AHF had similar age and sex distributions. However, 75% of AHF were African American, vs 58% of non-HF group. The initial mean (+-SD) systolic BP was clinically similar for AHF and non-HF, 210 +- 26 vs 205 +- 23 mm Hg (P = .008), respectively, with diastolic pressure being higher in the AHF cohort, 117 +- 24 vs 111 +- 23 (P b .0001).

Heart failure patients had more prior cardiac disease, hypertension, diabetes, chronic obstructive pulmonary disease, and renal dysfunction than did the non-HF population (see Table 1). Although the ejection fraction was slightly lower in the HF group (50% vs 55%; P b .0001), the HF cohort had a broader range (interquartile range, 16% vs 10%), and both fell within the range of preserved systolic function. Nonetheless, nearly 50% of AHF had a reduced ejection fraction vs only 25% of non-HF. Patients with AHF had higher troponin I and a median BNP nearly 5 times greater than non-HF. Troponin T and NTproBNP levels were similar between HF and non-HF, most likely from small numbers with these laboratory examinations performed (n = 55 and n = 41, respectively).

Table 2 shows HF patients had more atrial fibrillation and left ventricular hypertrophy, were more likely to require ICU admission, and receive bilevel positive pressure ventilation. Conversely, endotracheal intubations and other invasive procedures (except dialysis) were similar between HF and non-HF.

Acute HF patients were also more likely to receive oral therapy with ACEI or ARB, ?-blockers, hydralazine, diuretics, or nitrates before enrollment than non-HF,

AHF (n = 302)		Non-HF (n = 897)	P
Age, mean (SD)	59 (15)	57 (16)	.06
Male sex, n (%)	156 (52)	463 (52)	.99
Race, n (%)			b.0001
White	49 (16)	281 (31)
Black	226 (75)	522 (58)
Other	21 (7.0)	72 (8.0)
cardiac history, n (%)	195 (65)	361 (40)	b.0001
Myocardial infarction	56 (19)	121 (13)	.032
Congestive HF	153 (51)	156 (17)	b.0001
Hospitalization for HF	47 (16)	42 (4.7)	b.0001
Ejection fraction, median (interquartile range)	50 (39, 55)	55 (50, 60)	b.0001
Diabetes, n (%)	133 (44)	322 (36)	.013
Chronic obstructive pulmonary disease, n (%)	52 (17)	80 (8.9)	b.0001
Prior hypertension hospitalization, n (%)	136 (45)	261 (29)	b.0001
History of hypertension, n (%)	286 (95)	816 (91)	.040
Chronic kidney disease, n (%)	147 (49)	299 (33)	b.0001
Dialysis dependent, n (%)	62 (21)	104 (12)	b.0001
Admission laboratory examinations
BNP, pg/mL (median [interquartile range])	1020.0 (603.0, 2226.0)	231.1 (94.0, 495.0)	b.0001
NTpro-BNP, pg/mL (median [interquartile range])	3351.0 (1882.0, 5406.0)	7519.5 (230.6, 9999.9)	.60
Troponin T	0.04 (0.03, 0.10)	0.07 (0.03, 0.12)	.28
Troponin I	0.08 (0.04, 0.19)	0.06 (0.03, 0.15)	.015
Creatinine level, mg/dL (median [interquartile range])	1.9 (1.2, 4.5)	1.2 (1.0, 2.5)	b.0001

AHF (n = 302), n (%) Non-HF (n = 897), n (%) P
ICU admission Hospital length of stay, d (median [interquartile range]) Cardiac catheterization Dialysis Dialysis dependent at discharge Arterial line Mechanical ventilation Bilevel positive airway ventilation Chest x-ray Admission electrocardiogram Atrial fibrillation Left ventricular hypertrophy	152	(50)	308	(34)	b.0001
	4	(3, 8)	4	(2, 7)	.012
	24	(8.0)	83	(9.3)	.49
	59	(20)	84	(9.4)	b.0001
	44	(15)	61	(6.8)	b.0001
	47	(16)	133	(15)	.76
	38	(13)	90	(10)	.21
	22	(7.3)	9	(1.0)	b.0001
	297	(98)	757	(84)	b.0001
	297	(98)	804	(90)	b.0001
	20	(6.6)	34	(3.8)	.040
	108	(36)	235	(26)	.002

although they received similar rates of calcium channel blockers, ?-blockers, and clonidine. In the first day after hospitalization, the absolute rates of all antihypertensives increased for both cohorts; however, the trend of more use in HF continued for all medications except ?-blockers. Data for medication use is displayed in Table 3. We also found that in hypertensive HF patients BP control was not rapidly achieved. At 1 hour, only 29% of HF patients had a systolic BP less than 160 mm Hg, and by 6 hours, 74% still had systolic BP greater than 140 mm Hg.

Table 2 Resource use

We then dichotomized the population by the presence of end-organ damage. In the group without end-organ damage, AHF patients were nearly twice as likely to require ICU admission and had higher rehospitalization rates than non-HF cohort (see Table 4). However, among the population with end-organ damage, HF had little impact on outcomes.

Readmission at 30 days occurred in 26% and 21% (P =

.1013) of HF and non-HF, respectively. At 90 days, this occurred in 46% and 35% (P = .001), respectively. Table 5 describes the association of selected characteristics [7,11,14-17] with 90-day readmission. Readmission was

Table 3 Medications before admission to hospital and within 24 hours of admission

Medication received Medications before admission (oral) Medications within 24 h of admission

(intravenous or per os)

associated with higher initial, peak, and discharge creatinine, higher initial and discharge BNP, and higher discharge blood urea nitrogen levels.

To explore the association of decreasing BP and outcome, we evaluated composite outcomes as a function of time required to reach a systolic BP less than 120, 140, or 160 mm Hg, as shown in Table 6. Lowering the BP to 140 or 160 mm Hg had no relationship adverse outcomes, regardless of timing. Lowering the BP less than 120 mm Hg was associated with increased adverse events within 6 hours vs those with higher BPs (7.5% vs 16%; P = .029). The same relationship persisted at 12 hours. No other time points were associated with increased adverse events. Finally, no adverse composite outcome differences were based on the pharma- ceutical agent first used Table 7.

Discussion

Both hypertensive emergencies and HF are common hospital presentations, often occur simultaneously, and

	AHF, n (%)	Non-HF, n (%)	P		AHF, n (%)	Non-HF, n (%)	P
ACEI or ARB	149 (49)	339 (38)	b.001		169 (56)	380 (42)	b.0001
?-Blocker	165 (55)	409 (46)	.007		217 (72)	765 (85)	b.0001
Calcium channel blocker	91 (30)	227 (25)	.10		132 (44)	345 (38)	.11
?-Blocker	10 (3.3)	25 (2.8)	.64		17 (5.6)	29 (3.2)	.061
Hydralazine	33 (11)	59 (6.6)	.014		145 (48)	376 (42)	.06
Diuretic	128 (42)	224 (25)	b.0001		167 (55)	214 (24)	b.0001
Clonidine	50 (17)	144 (16)	.84		68 (23)	209 (23)	.78
Minoxidil	14 (4.6)	32 (3.6)	.40		12 (4.0)	18 (2.0)	.06
Other antihypertensives	8 (2.7)	29 (3.2)	.61		9 (3.0)	36 (4.0)	.41
Nitrates	52 (17)	84 (9.4)	b.001		170 (56)	293 (33)	b.0001

Table 4 Clinical outcomes New/worse end-organ damage a No end-organ damage
		AHF, n = 153	Non-HF, n = 373	P		AHF, n = 149	Non-HF, n = 524	P
	ICU admission, n (%)	88 (58)	183 (49)	.08		64 (43)	125 (24)	b.0001
	Median length of stay (interquartile range)	5 (3, 10)	5 (3, 9)	.27		3 (2, 6)	3 (1, 5)	.11
	In-hospital death, n (%)	9 (5.9)	22 (5.9)	.99		2 (1.3)	4 (0.8)	.62 b
	90-day hospitalization, n (%)	59 (45)	126 (39)	.22		68 (48)	158 (33)	.002
	Postdischarge death, n (%)	5 (3.7)	15 (4.6)	.68		6 (4.3)	16 (3.3)	.60 b
a Excluding acute pulmonary edema. b Fisher exact test used due to small cell values.

represent an important health burden. We report results from the STAT registry from patients with acute severe hyper- tension, 25.2% who presented with AHF. Although other studies have identified hypertension at ED presentation to be a low-risk predictor of 30-day death and readmission in the HF population [15] and suggested that this population may be appropriate for early discharge, our analysis did not support this.

Despite prior reports suggesting that initial presenting systolic BP is a low-risk predictor of adverse outcomes [18], we found that hypertensive HF patients have significant in- hospital mortality, commonly require ICU admission, frequently have prolonged hospital length of stay, and have a high likelihood of readmission. The differences in prior analyses indicating hypertensive HF as a low-risk predictor may result from our entry criteria of an intravenous antihypertensive agent selecting for a population with greater illness severity.

Patient characteristics

Age and sex were similar in our population of Hypertensive patients with or without HF. Half of our HF

Table 5 Predictors of readmission

population had a HF history, but only a small proportion had prior HF hospitalization. Most had preserved systolic function, as expected in the acute HF population [12].

Our hypertensive HF patients were more often African American, as has been reported in other analyses [5]. The high rate of African American representation has implica- tions in medication use. Overall, medication use in the hypertensive HF cohort was aligned with recommended HF therapies [19]; however, despite 75% of our hypertensive HF population were African Americans, only 11% (P = .014) of HF patients were taking hydralazine and 17% (P b .001) were on nitrates. Although this use was twice the non-HF use and the evidence for benefit is restricted to patients with reduced left ventricular ejection fraction who comprise a minority of our population, it is consistent with a general trend of poor adoption of this medication combination in African Americans.

Renal insufficiency at presentation is a well-known predictor of short- and long-term mortality in AHF [16]. We found that a significant proportion of hypertensive HF patients had an initially elevated creatinine level, and the peak level increased by 0.3 mg/dL, both of which were associated with increased readmissions. Three quarters of

Readmitted (n = 127)	Not readmitted (n = 147)		P
Blood urea nitrogen, median (interquartile range)
Admitting 28.0 (18.0, 45.0)	22.0	(17.0, 36.0)	.06
Discharge 29.0 (21.0, 44.0)	25.0	(19.0, 37.0)	.049
Creatinine level, median (interquartile range)
Admitting 2.1 (1.3, 5.6)	1.6	(1.2, 2.9)	.023
Peak 2.5 (1.5, 6.7)	2.0	(1.4, 3.8)	.031
Discharge 2.3 (1.4, 4.8)	1.7	(1.1, 3.2)	.009
Troponin I, median (interquartile range)
Admitting 0.09 (0.04, 0.20)	0.08	(0.03, 0.17)	.46
Peak 0.10 (0.05, 0.25)	0.10	(0.05, 0.29)	.80
BNP, median (interquartile range)
Admitting 1326.5 (796.8, 3105.5)	840.5	(507.0, 1536.0)	b.001
Discharge 1169.5 (622.0, 2453.0)	522.0	(282.0, 1197.0)	.002
NTpro-BNP, median (interquartile range)
Admitting 2766.7 (1402.0, 4426.0)	3331.8	(1904.5, 6205.0)	.44
Discharge 641.1 (641.1, 641.1)	2015.0	(167.0, 2611.2)	.77

blood pressure control and outcome”>Systolic BP has been	9 (4.6)	2 (1.9)	.34 a
b120 within 1 h
Systolic BP has been	18 (9.2)	4 (3.7)	.08
b120 within 2 h
Systolic BP has been	22 (11)	6 (5.6)	.10
b120 within 3 h
Systolic BP has been	32 (16)	8 (7.5)	.029
b120 within 6 h
Systolic BP has been	45 (23)	10 (9.4)	.003
b120 within 12 h
Only outcomes associated with a BP less than 120 mm Hg are shown, as lowering the BP to levels greater than 120 mm Hg were not associated with any statistical improvements in adverse clinical outcome rates. a Fisher exact test used due to the small cell values.

our HF population had a peak creatinine level of at least

Table 6 Blood pressure control over time among HF patients

Composite outcome (mechanical ventilation, ICU admission, hospital length of stay >=7 d, death at 30 d)

Yes (n = 195), No (n = 107), P

n (%) n (%)

1.5 mg/dL. Other HF analyses have demonstrated that as little as 0.2-mg/dL creatinine increase is associated with increased mortality [17]. This association may explain part of the increased mortality in hypertensive HF and suggests renal preservation may be an appropriate target for future management strategies. In addition, we do note that hypertensive HF patients were twice as likely to require dialysis than non-HF (20% vs 9.4%; P b .0001).

Resource use

We found that hypertensive patients with AHF require more resource use than many previously published HF analyses [5,6-8,11]. No subset of hypertensive HF patients had an ICU admission rate less than 40%, and AHF without end-organ injury had nearly double the rate of ICU admissions vs non-HF. Secondly, nearly one third of AHF required a hospital course longer than 1 week, also exceeding Prolonged hospitalizations reported in large HF registries [5,6-8,11]. Finally, no cohort of hypertensive HF patients

Variable	AHF, n (%)	Non-HF, n (%)		P
Mechanical ventilation	38 (13)	90	(10)	.21
ICU admission	152 (50)	308	(34)	b.0001
Length of stay >=7 d	93 (31)	234	(26)	.11
In-hospital death	11 (3.6)	26	(2.9)	.52
Death at 30 d	3 (1.0)	12	(1.3)	.77 a
a Fisher exact test used due to the small cell values.

had a 90-day readmission rate less than 45%. We suggest that hypertensive HF represents a unique cohort of patients with excessive resource use.

We noted a 7-fold higher use of bilevel positive pressure ventilation in AHF compared to non-HF. In contrast, AHF patients received mechanical ventilation at rates similar to non-HF. Although noninvasive airway support is an effective adjunct to avoid mechanical ventilation in decom- pensated HF [20,21], our database cannot evaluate its impact on the rate of mechanical ventilation we noted.

Blood pressure control and outcome

Many analyses describe a clinical benefit by lowering BP in patients presenting with HF. Most recently, in a small (n = 29) Prospective analysis, Levy et al [22] reported aggressive BP control with very high-dose nitroglycerin was associated with fewer ICU admissions and less endotracheal intubation than usual care in historical controls (n = 45). In an earlier observational study of 35 patients, Bosc et al [23] reported improvement in dyspnea and tachypnea in 71% of patients with BP lowered by a single 3000-ug bolus of Intravenous nitroglycerin. In the largest study (n = 110), Cotter et al [24] found a 21% decrease in the Composite end point of death, endotracheal intubation, or myocardial infarction in patients receiving bolus isosorbide dinitrate rather than furosemide. Sharon et al [25] also showed that death, endotracheal intubation, and myocardial infarction occurred more fre- quently in patients treated with bilevel positive airway pressure than those who received aggressive BP reduction therapy. Finally, in a placebo-controlled randomized HF trial, patients with a systolic BP of greater than 140 mm Hg and receiving relaxin had a modest BP reduction and improved clinical outcomes [26]. As these data suggest, rapid BP reduction for patients with acute pulmonary edema is associated with improved outcomes [27].

Our analysis is one of the largest to date evaluating BP control and outcomes among patients presenting with hypertensive HF (see Table 6). We describe what appears to be a limit in acutely lowering BP, as early excessive declines were associated with increases in the adverse composite outcome (see Table 7). Patients whose systolic BP was decreased to less than 120 mm Hg within 6 hours of enrollment had a rate of composite adverse events more than double that of those whose BP stayed greater than 120 mm Hg. Even at 1, 2, and 3 hours after enrollment, a trend for increased adverse events was noted for BPs less than 120 mm Hg, but this did not reach statistical significance, likely due to small numbers. By 12 hours, nearly 1 in 4 patients with a BP less than 120 mm Hg had a composite adverse event. This was in comparison to less than 1 in 10 patients having a composite adverse event if their systolic BP was greater than 120 mm Hg at 12 hours.

Table 7 Components of composite outcome

Because lowering BP less than 120 mm Hg within 12 hours was not associated with significant improvement in composite adverse event rates, this may represent a clinical

limit to BP reduction and suggests our outcomes may be consistent with recommendations to limit the initial BP reduction [28]. Alternatively, our findings may be a function of the small numbers of patients with early BP control or the result of confounding from composite adverse outcome parameter selection. Finally, our data should be considered in the context of previous smaller prospective studies noting clinical improvements with aggressive BP management [22-25,27].

Limitations

As a retrospective registry, causality cannot be deter- mined and our conclusions regarding the association of treatment and outcome are therefore hypothesis generating. Nevertheless, STAT is a large registry that suggests acute hypertensive HF should be regarded as a Serious condition associated with significant in hospital mortality and that excessive BP lowering may be associated with adverse events. A second limitation is that we defined the diagnosis of HF as pulmonary edema on chest x-ray or elevated Natriuretic peptides in the absence of renal failure. This may select for a cohort of patients with greater severity of illness than a clinically derived diagnosis. Although a cohort with greater severity of illness has the potential for more adverse events vs the general population, the objective nature of our HF definition will allow for accurate reproducibility and thus increase the probability of duplicating our results.

Conclusions

Acute HF patients with severe hypertension were similar to the non-HF acute hypertension cohort in age and sex but more commonly had a history of hypertension, renal insufficiency, and African American heritage. Excess resource use was required for a substantial proportion of AHF patients, as demonstrated by high rates of ICU admission, prolonged hospitalizations, and frequent 90-day readmissions. Finally, accurate BP control is critical, as declines below 120 mm Hg were associated with increased adverse event rates. Future Prospective trials are needed to determine the best therapy, timing, and BP target for patients presenting with hypertension and AHF.

References

1. Zampaglione B, Pascale C, Marchisio M, et al. Hypertensive urgencies and emergencies. Prevalence and clinical presentation. Hypertension 1996;27:144-7.
2. Kincaid-Smith P, Mc MJ, Murphy EA. The clinical course and pathology of hypertension with papilloedema (malignant hyperten- sion). Q J Med 1958;27:117-53.
3. Varon J, Marik PE. Clinical review: the management of hypertensive crises. Crit Care 2003;7:374-84.
4. Lip GY, Beevers M, Beevers DG. Complications and survival of 315 patients with malignant-phase hypertension. J Hypertens 1995;13:915-24.
5. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics 2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Committee. Circulation 2008;117; e25-146.
6. Hugli O, Braun JE, Kim S, et al. US ED visits for decompensated heart

failure, 1992-2001. Am J Cardiol 2005;96:1537-42.

1. Fonarow GC. Epidemiology and risk stratification in acute heart failure. Am Heart J 2008;155:200-7.
2. Adams KF, Fonarow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the US: rationale, design and preliminary observations from the first 100,000 cases in the acute decompensated heart failure National Registry [ADHERE]. Am Heart J 2005;149:209-16.
3. Solomon SD, Dobson J, Pocock S, et al. Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Investigators. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. Circulation 2007;116:1482-7.
4. Roguiin A, Behar D, Ben Ami H, et al. long-term prognosis of acute pulmonary edema-an ominous outcome. Eur J Heart Fail 2000;2: 137-44.
5. Fonarow GC, Stough WG, Abraham WT, et al. Characteristics, treatments and outcomes of patients with preserved systolic function hospitalized for heart failure: report from the OPTIMIZE-heart failure registry. J Am Coll Cardiol 2007;50:768-77.
6. Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O’Connor CM, She L, et al, for the OPTIMIZE-HF Investigators and Coordinators. Systolic Blood Pressure at Admission, Clinical Characteristics, and Outcomes in Patients Hospitalized With Acute Heart Failure. JAMA 2006;296:2217-26.
7. Katz JN, Gore JM, Amin A, Anderson FA, Dasta JF, Ferguson JF, Kleinschmidt K, Mayer SA, Multz AS, Peacock WF, Peterson E, Pollack C, Sung GY, Shorr A, Varon J, Wyman A, Emery LA, Granger CB, on behalf of the STAT Investigators. Practice Patterns, Outcomes, and End-Organ Dysfunction for Patients with Acute Severe Hypertension: The STAT Registry. Am Heart J 2009;158(4):599-606.
8. Fonarow GC, Heywood T, Heidenreich PA, et al. temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from the Acute Decom- pensated Heart Failure National Registry (ADHERE). Am Hear J 2007;153:1021-8.
9. Diercks DB, Peacock WF, Kirk JD, et al. outcome predictors in emergency department patients with heart failure: identification of a low-risk cohort. Crit Pathw Cardiol 2005;4(4):196.
10. Fonarow GC, Adams KF, Abraham WT, et al, for the ADHERE Scientific Advisory Committee, Study Group, and Investigators. Risk stratification for in-hospital mortality in Acutely decompensated heart failure: classification and regression tree analysis. JAMA 2005;293: 572-80.
11. Damman K, Navis G, Voors AA, Asselbergs FW, et al. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Cardiac Fail 2007;13:e599-608.
12. Adams KF, Lindenfeld J, for the Heart Failure Society of America. Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Cardiac Fail 2006;12(1):10-38.
13. Taylor AL, Ziesche S, Yancy C, et al, for the African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351: 2049-57.
14. Tallman TA, Peacock WF, Emerman CL, et al, for the ADHERE Registry. noninvasive ventilation outcomes in 2,430 acute decom- pensated heart failure patients: an ADHERE registry analysis. Acad Emerg Med 2008;15:1-8.
15. Collins SP, Mielniczuk LM, Whittingham HA, et al. The use of noninvasive ventilation in emergency department patients with acute

cardiogenic pulmonary edema: a systematic review. Ann Emerg Med 2006;48:260-9.

1. Levy P, Compton S, Welch R, et al. Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis. Ann Emerg Med 2007;50:144-52.
2. Bosc E, Bertinchant JP, Hertault J. The use of injectable nitroglycerin (a bolus of 3 mg) in the treatment of cardiogenic pulmonary edema. Ann Cardiol Angeiol (Paris) 1982;31:477-80.
3. Cotter G, Metzkor E, Kaluski E, et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet 1998;351:389-93.
4. Sharon A, Shpirer I, Kaluski E, et al. High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation

combined with Conventional treatment for severe pulmonary edema. J Am Coll Cardiol 2000;36:832-7.

1. Teerliink J, Metra M, Felker G, Ponikowski P, Voors A, Weatherley B, Marmor A, Katz A, Grzybowski J, Unemon E. Relaxin for the treatment of patients with acute heart failure (pre- RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet 2009;373 (9673):1429-39.
2. Cotter G, Moshkovitz Y, Kaluski E, et al. The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with Acute congestive heart failure. Eur J Heart Fail 2003;5: 443-51.
3. Haas AR, Marik PE. Current diagnosis and management of hypertensive emergency. Semin Dial 2006;19(6):502-12.