| Background and objectiveNearly half of the patients with acute heart failure(HF)have residual congestion before discharge,which is associated with an increased risk of post-discharge death or readmission,especially in patients with renal dysfunction.There are two forms of congestion depending on whether it is mainly found in the vascular system(intravascular congestion)or the interstitium(tissue congestion).Thoracic fluid content(TFC)or TFC index(TFCI)measured by impedance cardiography could be used to evaluate pulmonary congestion quantitatively.The relationships between TFC and long-term clinical outcomes and quality of life in patients with acute HF remain unclear.Little is known about the post-discharge congestion status,especially intravascular congestion and tissue congestion,and their relationships with prognosis.And there is no single indication to reflect the combined effects of residual congestion and renal dysfunction.The aims of this study were to:(1)explore the association of pre-discharge TFC level with the risk of long-term death or rehospitalization and short-term quality of life in patients with acute HF;(2)analyze residual congestion status classified by intravascular and tissue congestion at one month after discharge and its association with the risk of long-term death or rehospitalization;(3)propose a quantitative indicator to assess the status of predischarge congestion with renal dysfunction and to explore its association with the risk of long-term death or rehospitalization and its incremental prognostic value compared with the established scoring systems.MethodsWe enrolled patients aged 18 years or older who were admitted for HF to eight hospitals in China from September 2016 to May 2018.Impedance cardiography was performed they reached the stable period of their hospitalization and at one month after discharge.Information on death or rehospitalization was collected via interview or telephone after discharge.The key exposures of this study were:(1)TFC level in the stable period during hospitalization;(2)intravascular and tissue congestion at one month assessed by the relative change of N-Terminal pro-B-type natriuretic peptide from admission to one month of discharge and TFC level at one month,respectively;(3)congestion and renal index(CRI,i.e.,ratio of TFCI to glomerular filtration rate)in the stable period during hospitalization.The outcomes included quality of life assessed by the Kansas City Cardiomyopathy Questionnaire one month after discharge and clinical outcomes(one-year death or rehospitalization,four-year death).Statistical analysis methods included:(1)Restricted cubic spline curves were used to explore the non-linear association between stable TFC levels and clinical outcomes.Cox proportional risk models and linear regression models were used to explore the association between different TFC levels and clinical outcomes and quality of life,respectively;(2)Cox proportional risk model was used to explore the association between congestion status at one month after discharge and clinical outcomes;(3)The relationships between CRI and clinical outcomes were explored using inverse probability treatment weighting.The incremental prognostic value of CRI added to established risk scoring systems was assessed by net reclassification improvement and integrated discrimination improvement.ResultsIn the analysis of stable TFC,a total of 990 patients were included.The mean age of patients was 63 years and 40%were female.484(48.9%)patients suffered one-year all-cause death or rehospitalization.391(39.5%)patients suffered four-year all-cause death.The risk of one-year all-cause death or rehospitalization in patients with TFC>50/KΩ was 53%higher than those with TFC≤35/KQ(hazard ratio[HR]1.53,95%confidence interval[CI]1.10-2.12).The risk of four-year death in patients with TFC>50/KΩ was 1.07 times higher than those with TFC≤35/KΩ(HR 2.07,95%CI 1.45-2.95).No heterogeneity was found in the associations between TFC levels and clinical outcomes in most subgroups.The Kansas City Cardiomyopathy Questionnaire score at one month after discharge in patients with TFC>50/KQ was 5.71 points(β-5.71,95%CI-9.67—-1.75)lower than that in patients with TFC≤3 5/KΩ.In the analysis of congestion status at one month of discharge,a total of 649 patients were included.The mean age of patients was 61 years,and 37%were female;162(25.0%)had intravascular congestion alone,120(18.5%)tissue congestion alone,and 204(31.4%)combined intravascular and tissue congestion at one month after discharge.161(24.8%)patients suffered one-year cardiovascular death or HF rehospitalization.201(31.0%)patients suffered four-year death.Compared with patients without congestion,those with combined intravascular and tissue congestion had a statistically significant 2.6-fold risk of one-year cardiovascular death or HF rehospitalization(2.64,95%CI 1.62-4.29),those with intravascular congestion alone or tissue congestion alone had a non-significantly higher risk of one-year cardiovascular death or HF rehospitalization.Compared with patients without congestion,those with intravascular congestion alone(HR 2.01,95%CI 1.23-3.28),tissue congestion alone(HR 2.84,95%CI 1.74-4.62)and combined intravascular and tissue congestion(HR 2.59,95%CI 1.66-4.03)had a significantly higher risk of four-year death(P<0.05).In the analysis of stable CRI,a total of 939 patients were included(mean age 63 years,39%female).279(29.7%)patients suffered one-year HF rehospitalization and 369(39.3%)patients suffered four-year death.Compared with patients with CRI≤0.59 ml/min/KΩ,those with CRI>0.59 ml/min/KΩ had a 39%higher risk of one-year HF rehospitalization(HR 1.39,95%CI 1.01-1.89)and an 85%higher risk of four-year death(HR 1.85,95%CI 1.38-2.47).And CRI had an incremental prognostic value compared with the established scoring system(net reclassification improvement>0,integrated discrimination improvement>0,P<0.05).ConclusionsAmong patients with acute HF,patients with stable TFC>50/KQ had a 50%increased risk of one-year all-cause death or rehospitalization and twice the risk of fouryear death compared with those with TFC≤ 5/KΩ.The associations were not significantly different among subgroups.Patients with TFC>50/KΩ had poorer quality of life at one month after discharge than those with TFC≤35/KΩ.Up to one-third of acute HF patients had combined intravascular and tissue congestion at one month after discharge and a significantly higher risk of rehospitalization or death than those without congestion.Stable CRI is independently associated with death or hospitalization and improves the risk stratification of the established risk models.These results suggest that continuous monitoring of residual congestion status could be instructive for timely titration or modification of treatment regimens in patients with acute HF. |
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