Identification of Patient Phenotypes Associated With Elevated Aldosterone Levels
Post-discharge mortality and re-hospitalization for acute heart failure (AHF) affects 15% and 30% of patients respectively, within 90 days. With over 1 million annual hospitalizations and a financial cost exceeding 20 billion dollars, AHF is a major public health burden. Yet no AHF therapy to date definitively reduces morbidity and mortality, and in stark contrast to heart attack patients, highly rated evidence in guidelines do not exist. Although AHF is a syndrome and not one disease, typical treatment of patients hospitalized with AHF suggests otherwise. Despite substantial differences among AHF patients, therapy is largely uniform; patients receive medicine to help get rid of excess volume and little else. Although decades of empirical use support the symptomatic benefits of traditional therapies, outcomes remain extremely poor. As opposed to the "one-size-fits-all‟ approach used unsuccessfully to date in clinical trials, identification of specific AHF patient sub-groups is critical, so that tailored therapies can be developed and tested. Preliminary data suggests that the neurohormone aldosterone may be detrimental in AHF patients. Furthermore, this hormone level appears to rise during hospitalization. The investigators therefore propose to identify specific AHF patient phenotypes associated with high serum aldosterone levels to subsequently address the hypothesis that early aldosterone blockade continued throughout hospitalization will decrease re-hospitalization and mortality. Specifically, the investigators hypothesize that AHF patients with elevated serum aldosterone levels have a distinct phenotype compared to those with lower or normal aldosterone levels. Specifically, they will be older, have a lower systolic blood pressure, lower EF, worse renal function, higher BNP, and previous hospitalization for HF.
Acute Heart Failure
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Identification of Patient Phenotypes Associated With Elevated Aldosterone Levels|
- There is no prespecified primary outcome as this is an exploratory study [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- There is no secondary outcome as this is an exploratory study [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To prospectively examine the baseline and dynamic phenotype of AHFS patients in relation to aldosterone levels on initial presentation. [ Time Frame: two years ] [ Designated as safety issue: No ]
Hypothesis 2.1: The "high aldosterone" phenotypic profile identified in Aim 1 will be associated with high aldosterone levels on initial presentation to the ER in our prospective replication study.
Hypothesis 2.2: AHFS patients with high aldosterone levels on presentation will have increased high-sensitivity troponin release and echocardiographic markers of increased myocardial and atrial fibrosis.
Hypothesis 2.3: Repeat examination at 48 hours after initial presentation will demonstrate lack of improvement in laboratory and echocardiographic biomarkers of congestion, myocyte injury, and fibrosis in AHFS patients with high aldosterone levels, suggesting a time-sensitive component to aldosterone antagonism in AHFS.
Biospecimen Retention: Samples Without DNA
Plasma storage for potential future studies with existing or novel biomarkers.
|Study Start Date:||May 2012|
|Study Completion Date:||June 2014|
|Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01614860
|United States, Illinois|
|Northwestern Memorial Hospital|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||Peter S Pang, MD||Northwestern University|