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Hypotension during hospitalization for acute heart failure is independently associated with 30-day mortality: findings from ASCEND-HF.

ABSTRACT: Outcomes associated with episodes of hypotension while hospitalized with acute decompensated heart failure are not well understood.Using data from Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF), we assessed factors associated with in-hospital hypotension and subsequent 30-day outcomes. Patients were classified as having symptomatic or asymptomatic hypotension. Multivariable logistic regression was used to determine factors associated with in-hospital hypotension, and Cox proportional hazards models were used to assess the association between hypotension and 30-day outcomes. We also tested for treatment interaction with nesiritide on 30-day outcomes and the association between in-hospital hypotension and renal function at hospital discharge. Overall, 1555 of 7141 (21.8%) patients had an episode of hypotension, of which 73.1% were asymptomatic and 26.9% were symptomatic. Factors strongly associated with in-hospital hypotension included randomization to nesiritide (odds ratio, 1.98; 95% confidence interval [CI], 1.76-2.23; P<0.001), chronic metolazone therapy (odds ratio, 1.74; 95% CI, 1.17-2.60; P<0.001), and baseline orthopnea (odds ratio, 1.31; 95% CI, 1.13-1.52; P=0.001) or S3 gallop (odds ratio, 1.21; 95% CI, 1.06-1.40; P=0.006). In-hospital hypotension was associated with increased hazard of 30-day mortality (hazard ratio, 2.03; 95% CI, 1.57-2.61; P<0.001), 30-day heart failure hospitalization or mortality (hazard ratio, 1.58; 95% CI, 1.34-1.86; P<0.001), and 30-day all-cause hospitalization or mortality (hazard ratio, 1.40; 95% CI, 1.22-1.61; P<0.001). Nesiritide had no interaction on the relationship between hypotension and 30-day outcomes (interaction P=0.874 for death, P=0.908 for death/heart failure hospitalization, P=0.238 death/all-cause hospitalization).Hypotension while hospitalized for acute decompensated heart failure is an independent risk factor for adverse 30-day outcomes, and its occurrence highlights the need for modified treatment strategies.http://www.clinicaltrials.gov. Unique identifier: NCT00475852.

SUBMITTER: Patel PA

PROVIDER: S-EPMC4456178 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Hypotension during hospitalization for acute heart failure is independently associated with 30-day mortality: findings from ASCEND-HF.

Patel Priyesh A PA Heizer Gretchen G O'Connor Christopher M CM Schulte Phillip J PJ Dickstein Kenneth K Ezekowitz Justin A JA Armstrong Paul W PW Hasselblad Vic V Mills Roger M RM McMurray John J V JJ Starling Randall C RC Tang W H Wilson WH Califf Robert M RM Hernandez Adrian F AF

Circulation. Heart failure 20141003 6

<h4>Background</h4>Outcomes associated with episodes of hypotension while hospitalized with acute decompensated heart failure are not well understood.<h4>Methods and results</h4>Using data from Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF), we assessed factors associated with in-hospital hypotension and subsequent 30-day outcomes. Patients were classified as having symptomatic or asymptomatic hypotension. Multivariable logistic regression was used ...[more]

PMID: 25281655

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Project description:ObjectivesThis study sought to determine the degree to which U.S. patients enrolled in a heart failure (HF) trial represent patients in routine U.S. clinical practice according to race and sex.BackgroundBlack patients and women are frequently under-represented in HF clinical trials. However, the degree to which black patients and women enrolled in trials represent such patients in routine practice is unclear.MethodsThe ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized patients hospitalized for HF to receive nesiritide or placebo from May 2007 to August 2010 and was neutral for clinical endpoints. This analysis compared non-Hispanic white (n = 1,494) and black (n = 1,012) patients enrolled in ASCEND-HF from the U.S. versus non-Hispanic white and black patients included in a U.S. hospitalized HF registry (i.e., Get With The Guidelines-Heart Failure [GWTG-HF]) during the ASCEND-HF enrollment period and meeting trial eligibility criteria.ResultsAmong 79,291 white and black registry patients, 49,063 (62%) met trial eligibility criteria (white, n = 37,883 [77.2%]; black, n = 11,180 [22.8%]). Women represented 35% and 49% of the ASCEND-HF and trial-eligible GWTG-HF cohorts, respectively. Compared with trial-enrolled patients, trial-eligible GWTG-HF patients tended to be older with higher blood pressure and higher ejection fraction. Trial-eligible patients had higher in-hospital mortality (2.3% vs. 1.3%), 30-day readmission (20.2% vs. 16.8%), and 180-day mortality (21.2% vs. 18.6%) than those enrolled in the trial (all p < 0.02), with consistent mortality findings by race and sex. After propensity score matching, mortality rates were similar; however, trial-eligible patients continued to have higher rates of 30-day readmission (23.1% vs. 17.3%; p < 0.01), driven by differences among black patients and women (all p for interaction ≤0.02).ConclusionsPatients with HF seen in U.S. practice and eligible for the ASCEND-HF trial had worse clinical outcomes than those enrolled in the trial. After accounting for clinical characteristics, trial-eligible real-world patients continued to have higher rates of 30-day readmission, driven by differences among black patients and women. Social, behavioral, and other unmeasured factors may impair representativeness of patients enrolled in HF trials, particularly among racial/ethnic minorities and women. (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF]; NCT00475852).

Project description:BackgroundHeart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking.MethodsThe genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered P<5×10-8.ResultsCommon variants (rs2342882 and rs35850039 in complete linkage disequilibrium) located in FGD5 were significantly associated with the primary outcome in both ancestry groups (European Americans: hazard ratio [HR], 1.38; P=2.42×10-6; African ancestry: HR, 1.51; P=4.43×10-3; HR in meta-analysis, 1.41; P=4.25×10-8). FGD5 encodes a regulator of VEGF (vascular endothelial growth factor)-mediated angiogenesis, and in silico investigation revealed several previous genome-wide association study hits in this gene, among which rs748431 was associated with our outcome (HR, 1.20; meta P<0.01). Sensitivity analysis proved FGD5 common variants survival association did not appear to operate via coronary artery disease or nesiritide treatment (P>0.05); and the signal was still significant when changing the censoring time from 180 to 30 days (HR, 1.39; P=1.59×10-5).ConclusionsIn this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in FGD5 were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether FGD5 could be a therapeutic target.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT00475852.

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Hypotension during hospitalization for acute heart failure is independently associated with 30-day mortality: findings from ASCEND-HF.

Publications

Hypotension during hospitalization for acute heart failure is independently associated with 30-day mortality: findings from ASCEND-HF.

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