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2012
analysis Global Group in Chronic Heart Failure (MAGGIC) Investigators Background-Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. Methods and Results-We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146 -155), 10 589 (51%) and 11 422 (55%) had an eGFR Ͻ60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%-5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Conclusions-Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF. (Circ Heart Fail. 2012;5:309-314.) The online-only Data Supplement is available at http://circheartfailure.ahajournals.org/lookup/suppl/
Interrelation between heart failure with preserved ejection fraction and renal impairment
Reviews in Cardiovascular Medicine, 2022
Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) are global diseases of increasing prevalence and are frequent co-diagnoses. The two conditions share common risk factors and CKD contributes to HFpEF development by a variety of mechanisms including systemic inflammation and myocardial fibrosis. HFpEF patients with CKD are generally older and have more advanced disease. CKD is a poor prognostic indicator in HFpEF, while the impact of HFpEF on CKD prognosis is not sufficiently investigated. Acute kidney injury (AKI) is common during admission with acute decompensated HFpEF, but short and long-term outcomes are not clear. Pharmacological treatment options for HFpEF are currently minimal, and even more so limited in the presence of CKD with hyperkalaemia being one of the main concerns encountered in clinical practice. Recent data on the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of HFpEF are encouraging, especially in light of the abundance of evidence supporting improved renal outcomes. Herein, we review the pathophysiological links between HFpEF and CKD, the clinical picture of dual diagnosis, as well as concerns with regards to renal impairment in the context of HFpEF management.
The Significance of Serum Urea and Renal Function in Patients With Heart Failure
Medicine, 2010
Renal function and urea are frequently abnormal in patients with heart failure (HF) and are predictive of increased mortality. The relative importance of each parameter is less clear. We prospectively compared the predictive value of renal function and serum urea on clinical outcome in patients with HF. Patients hospitalized with definite clinical diagnosis of HF (n = 355) were followed for short-term (1 yr) and long-term (mean, 6.5 yr) survival and HF rehospitalization. Increasing tertiles of discharge estimated glomerular filtration rate (eGFR) were an independent predictor of increased long-term survival (hazard ratio EHR^, 0.65; 95% confidence interval ECI^, 0.47Y0.91; p = 0.01) but not short-term survival. Admission and discharge serum urea and blood urea nitrogen (BUN)/creatinine ratio were predictors of reduced short-and long-term survival on multivariate Cox regression analysis. Increasing tertiles of discharge urea were a predictor of reduced 1-year survival (HR, 2.13; 95% CI, 1.21Y3.73; p = 0.009) and long-term survival (HR, 1.93; 95% CI, 1.37Y2.71; p G 0.0001). Multivariate analysis including discharge eGFR and serum urea demonstrated that only serum urea remained a significant predictor of longterm survival; however, eGFR and BUN/creatinine ratio were both independently predictive of survival. Urea was more discriminative than eGFR in predicting long-term survival by area under the receiver operating characteristic curve (0.803 vs. 0.787; p = 0.01). Increasing tertiles of discharge serum urea and BUN/creatinine were independent predictors of HF rehospitalization and combined death and HF rehospitalization. This study suggests that serum urea is a more powerful predictor of survival than eGFR in patients with HF. This may be due to urea_s relation to key biological parameters including renal, hemodynamic, and neurohormonal parameters pertaining to the overall clinical status of the patient with chronic HF.
International Journal of Cardiology, 2013
Objective: To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF). Background: It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brainnatriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF. Methods: Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed. Results: Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m 2 (18-157). A total of 252 patients died. All five biomarkerslog(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P b 0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P b 0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P b 0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P = 0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P b 0.001)were associated with mortality risk, but not affected by RD (P N 0.05 for all interactions). Conclusion: Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.
Clinical outcome of renal tubular damage in chronic heart failure
European Heart Journal, 2011
Both reduced glomerular filtration and increased urinary albumin excretion independently determine outcome in patients with chronic heart failure (HF). However, tubulo-interstitial injury might indicate renal damage, even in the presence of normal glomerular filtration. We studied the relationship between tubular damage, glomerular filtration, urinary albumin excretion, and outcome in HF patients. Methods and results In 2130 patients participating in the GISSI-HF trial, we measured urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and three urinary markers of tubular damage: N-acetyl-beta-D-glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). We assessed the relationship between the individual tubular damage markers and the combined endpoint of all-cause mortality and HF hospitalizations. Mean age was 67 + 11 years, and 21% were female. Urinary NAG 13.7 (7.8-22) U/gCr, KIM-1 1939 (671-3871) ng/gCr, and NGAL 36 (14-94) mg/gCr were markedly elevated above normal levels. All individual tubular markers were independently associated with the combined endpoint: NAG: adjusted hazard ratio (HR) 1.22; 95% confidence interval (CI), 1.10-1.36; P , 0.001, KIM-1 HR 1.13; 95% CI, 1.02-1.24; P ¼ 0.018 and NGAL HR 1.10; 95% CI, 1.00-1.20; P ¼ 0.042; all per log standard deviation increase). Even in patients with a normal eGFR, increased tubular markers were related to a poorer outcome. The combination of impaired eGFR, increased UACR, and high NAG was associated with a HR of 3.00; 95% CI, 2.29-3.95; P , 0.001, compared with those without these abnormalities. Conclusion Tubular damage is related to a poor clinical outcome in HF patients even when eGFR is normal. ClinicalTrials.gov Identifier: NCT00336336 (for the main study).
Circulation: Cardiovascular Quality and Outcomes, 2013
H eart failure (HF) currently affects ≈5.7 million adults in the United States and is associated with an estimated $29 billion in hospital charges annually. 1 Driven by a variety of factors, the prevalence of HF is a current and increasing public health problem nationally and internationally. Many patients with HF also have chronic kidney disease (CKD), most frequently manifest as a reduced glomerular filtration rate (GFR), and the risk of developing HF is substantially increased with worsening stage of CKD. 2 Many of the same factors contribute to the development of both chronic diseases, including age, diabetes mellitus, and hypertension. 2,3 Although patients with HF suffer poor outcomes, including a death rate of ≈50% within 5 years of diagnosis, 1 the co-occurrence of CKD and HF seems to confer an even higher rate of poor outcomes, especially in those with HF and reduced left ventricular ejection fraction (HF-REF). 4 The physiological relations between CKD and HF are multifactorial and causally intertwined. For example, kidney dysfunction contributes to HF by increased salt retention and volume expansion, upregulation of neurohormonal pathways, proinflammatory mechanisms, and likely other mechanisms. HF worsens CKD by decreasing renal perfusion and activation of the catecholaminergic and renin-angiotensin-aldosterone system. 5-7 In addition, both CKD and HF can cause or worsen other comorbid conditions, including anemia, 8 coronary and peripheral atheroschlerosis, 9 and malnutrition. 10 Because the population prevalence of HF has increased, so has the proportion of patients with HF preserved left ventricular EF (HF-PEF). 11 Few studies have, however, examined how CKD affects clinically meaningful outcomes among patients with HF-PEF. Existing data have largely come from studies Background-There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF). Methods and Results-We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m 2 , lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m 2 and 7× higher for eGFR<15 mL/min per 1.73 m 2 , with similar findings in those with HF with reduced left ventricular EF. Conclusions-CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective inter ventions for the growing number of patients with HF complicated by CKD.
Current Cardiovascular Risk Reports, 2012
Generic chronic kidney disease (CKD) can be defined by a lowered estimated glomerular filtration rate (eGFR) and/or "kidney damage," the latter by abnormal albuminuria (>30 mg/d), imaging, urinalysis, or renal pathology, that persists for at least 3 months. According to current schema, any adult with an eGFR <60 mL/min/ 1.73 m 2 for 3 months or longer can be regarded as having CKD. This definition may be to all-encompassing and lead to over-diagnosis in some groups (particularly the elderly). It is currently undergoing a refinement. Although eGFR and albuminuria are principally used to define CKD and stratify its prognosis, a number of new biomarkers, such as NGAL, FGF-23, Cystatin C, uric acid, and ADMA are emerging that may have utility in enhancing the accuracy of predicting cardiovascular risk in CKD. As currently defined, CKD has important implications for the future risk of cardiovascular events. Albuminuria and lowered eGFR both contribute independently to the associations with cardiovascular risk. Albuminuria does so in a continuous log-linear manner whereas eGFR demonstrates a threshold effect (at around 45-60 mL/min/1.73 m 2). The precise mechanisms underlying these associations are complex and poorly understood, but enhanced atherogenesis, diffuse endothelial injury, and left ventricular hypertrophy are important factors. Left ventricular hypertrophy is a major risk factor for congestive heart failure and sudden cardiac death in advanced CKD and it may become a specific target for interventions in the future, especially as the role of elevation in serum FGF-23 levels in the genesis of left ventricular hypertrophy are better understood.
Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure
Circulation, 2006
on behalf of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Investigators Background-Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. Methods and Results-The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (Յ40%) or preserved LVEF (Ͼ40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 mol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR Ͻ60 mL/min per 1.73 m 2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m 2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m 2 and 1.86 for Ͻ45 mL/min per 1.73 m 2 for the primary outcome, both PϽ0.001, and hazard ratio of 1.50, Pϭ0.006, and 1.91, Pϭ0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Conclusions-Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR. (Circulation. 2006;113:671-678.)
European heart journal. Acute cardiovascular care, 2015
Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent diffe...