口服袢利尿剂剂量与慢性心力衰竭全因死亡率的关系

目的研究口服袢利尿剂剂量与慢性心力衰竭(心衰)患者全因死亡率的关系。方法入选并随访1197例(1120例获得用药资料)慢性心衰患者.男性占81.7%,平均年龄56.5±13.6岁,平均左室射血分数(LVEF)35.6±8.9%;全因死亡为随访终点。先比较不同口服袢利尿剂剂量(0、≤20、20～40、>40mg/日呋塞米当量)人群其他预后相关因素分布的差异,再应用Kaplan-Meier曲线及Log-rank检验对不同剂量人群的生存率进行描述及比较,多元Cox回归用于分析口服袢利尿剂剂量是否为心衰死亡的独立预测因子。结果完成随访1025例(失访率14.4%),死亡360例(35.1%);随访中位数44个月。平均袢利尿剂剂量34.26±2.67mg/日呋塞米当量。应用不同袢利尿剂剂量的心衰患者在合并症、血压、LVEF、多种检验项目及用药方面存在显著差异。不同剂量心衰人群的死亡率分别为19.2%、29.6%、39.8%及55.4%,随着袢利尿剂应用剂量增加而增高(P<0.001);校正其他影响因素后,口服袢利尿剂剂量与心衰患者不良预后独立相关。剂量每增加10mg/日呋塞米当量,心衰死亡风险增加1.072倍(P<0.001)。服用≤20mg/日、20-40mg/日及>40mg/日呋塞米当量心衰人群的死亡风险分别是未服用者的1.575倍(P=0.023)、1.958倍(P=0.001)及2.543倍(P<0.001)。结论虽然年龄、体重指数、LVEF、合并室速、是否应用血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂、应用袢利尿剂剂量、血红蛋白、总胆红素、尿酸均与心衰预后相关。应用袢利尿剂且随着剂量增加,心衰的死亡风险增高。     

The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure

Aims

Diuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness.

Methods and results

We conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naïve: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol-derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naïve group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naïve versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03–35.89] vs. 29.70 [18.19–34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naïve versus chronic users, that is the urine volume per 1 μg/ml of urine furosemide at 2 h was 148.6 ± 136.1 versus 50.6 ± 56.1 ml (p = 0.005).

Conclusions

Patients naïve to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.     

Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes – from the ESC-HFA EORP Heart Failure Long-Term Registry

Aims

To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes.

Methods and results

Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35–1.89), Yes/No 1.35 (1.14–1.59), and No/Yes 1.18 (0.96–1.45). For death or heart failure hospitalization they were 1.38 (1.21–1.58), 1.17 (1.02–1.33), and 1.09 (0.93–1.27), respectively.

Conclusion

Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk.     

Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial

BACKGROUND: We examined the relation of maximal in-hospital diuretic dose to weight loss, changes in renal function, and mortality in hospitalised heart failure (HF) patients. METHODS: In ESCAPE, 395 patients received diuretics in-hospital. Weight was measured at baseline, discharge, and every other day before discharge. Weight loss was defined as the difference between baseline and last in-hospital weight. Mortality was assessed using a log-logistic model with non-zero background. RESULTS: Median weight loss: 2.8 kg (0.7, 6.1); mean: 3.7 kg (22% of values <0). Weight loss and maximum in-hospital dose were correlated (p=0.0007). Baseline weight, length of stay, and baseline brain natriuretic peptide were significant predictors of weight loss. After adjusting for these, dose was not a significant predictor of weight loss. A strong relation between dose and mortality was seen (p=0.003), especially at >300 mg/day. Dose remained a significant predictor of mortality after adjusting for baseline variables that significantly predicted mortality. Correlation between maximal dose and creatinine level change was not significant (r=0.043; p=0.412) CONCLUSIONS: High diuretic doses during HF hospitalisation are associated with increased mortality and poor 6-month outcome.     

Hemoconcentration is a good prognostic predictor for clinical outcomes in acute heart failure: Data from the Korean Heart Failure (KorHF) Registry

Background

Hemoconcentration is a surrogate marker of effective decongestion and diuresis therapy. Recently, hemoconcentration has been associated with decreased mortality and rehospitalization in heart failure (HF) patients. However, the prognostic power of hemoconcentration in a large sample-sized HF cohort was limited until now.

Methods and results

We analyzed data from hospitalized patients with acute heart failure (AHF) that were enrolled in the Korean Heart Failure Registry(n = 2,357). The primary end point was a composite of all-cause mortality and HF rehospitalization during the follow-up period (median = 347, interquartile range = 78–744 days).Hemoconcentration, defined as an increased hemoglobin level between admission and discharge, was presented in 1,016 AHF patients (43.1%). In multivariable logistic regression, hemoglobin, total cholesterol, and serum glucose levels at admission, and ischemic HF, were significant determinants for hemoconcentration occurrence. The Kaplan–Meier curve showed that event-free survival was significantly higher in the hemoconcentration group compared to the non-hemoconcentration group (65.1% vs. 58.1%, log rank p < 0.001). In multiple Cox proportional hazard analysis, hemoconcentration was an independent predictor of the primary end point after adjusting for other HF risk factors (hazard ratio = 0.671, 95% confidence interval = 0.564–0.798, p < 0.001).

Conclusions

Hemoconcentration during hospitalization was a prognostic marker of fewer clinical events in the AHF cohort. Therefore, this novel surrogate marker will help in the risk stratification of AHF patients.     

Antigen carbohydrate 125 and creatinine on admission for prediction of renal function response following loop diuretic administration in acute heart failure

Background

The use of loop diuretics in acute heart failure (AHF) is largely empirical and has been associated with renal function impairment by reducing renal perfusion but also renal improvement by decreasing renal venous congestion. Antigen carbohydrate 125 (CA125) has emerged as a proxy for fluid overload. We sought to evaluate whether the early changes in creatinine (ΔCr) induced by intravenous furosemide doses (ivFD) differ among clinical groups defined by overload status (CA125) and creatinine on admission (Cr).

Methods and results

We included 526 consecutive patients admitted for AHF. All patients received intravenous furosemide for the first 48 hours. CA125 and Cr were dichotomized at 35 U/ml and 1.4 mg/dl, respectively, and grouped as follows: C1 [Cr < 1.4, CA125 ≤ 35 (n = 151)]; C2 [Cr < 1.4, CA125 > 35 (n = 241)]; C3 [Cr ≥ 1.4, CA125 ≤ 35 (n = 45)]; and C4 [Cr ≥ 1.4, CA125 > 35 (n = 89)]. Clinicians in charge of the management of patients were blind to CA125 values. ΔCr was estimated as the absolute difference in Cr between admission and 48–72 hours. Multivariable linear regression analysis was used for modeling purposes. The adjusted analysis showed a differential effect of ivFD on ΔCr. Per increase in 20 mg/day of ivFD, the mean ΔCr was 0.010 mg/dl (p = 0.464) in C1, 0.002 mg/dl (p = 0.831) in C2, 0.045 mg/dl (p = 0.032) in C3, and − 0.045 mg/dl (p < 0.001) in C4 (omnibus p < 0.001). A similar pattern of response was observed in a validation cohort.

Conclusions

In patients with AHF, the magnitude and direction of ΔCr attributable to ivFD were differentially associated with values of CA125 and Cr on admission.