Abstract
BackgroundIn previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan–Meier analysis was used to investigate the importance of the combinations. MethodsIn a multi-centre observational trial, we prospectively enrolled 213 patients with HF who were hospitalized because of exacerbation, discharged according to HF treatment guidelines and observed to monitor cardiovascular events. After the observation period, we stratified patients according to whether they experienced cardiovascular events (rehospitalisation or cardiovascular death). FindingsAmong 77,562 combinations of fewer than five clinical parameters, we identified 151 combinations that could potentially explain the occurrence of cardiovascular events. Of these, 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. Importantly, Kaplan–Meier curves demonstrated that the use of inotropes or of diuretics without bradycardia or tachycardia were independent predictors of a markedly worse cardiovascular prognosis. InterpretationPatients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF.
Highlights
Cardiovascular disease has placed a significant burden both on individual patients and national economies [1, 2]
Using the limitless-arity multiple-testing procedure (LANP) method for the patients with heart failure (HF), we found that the patients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events, which are novel finding on the top of the conventional knowledge of the current HF treatment strategy
In our analysis of 77,562 combinations with no N4 clinical parameters, we identified 151 combinations involving 54 parameters that predicted the occurrence of cardiovascular events (Table 3)
Summary
Cardiovascular disease has placed a significant burden both on individual patients and national economies [1, 2]. Several biomarkers, including blood levels of brain natriuretic peptide (BNP) [7], C-reactive protein [8] and albumin [9], have been measured in patients with HF with the aim of determining the severity and probability of cardiovascular events Various drugs, such as angiotensin-converting inhibitors [10], diuretics [11] and inotropic agents [12], have been administered to patients with the intent to improve the pathophysiology of HF. 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF
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