Chronic kidney disease and cardiac remodelling in patients with mild heart failure: Results from the REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE) study

Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA, USA.
European Journal of Heart Failure (Impact Factor: 6.53). 09/2012; 14(12). DOI: 10.1093/eurjhf/hfs135
Source: PubMed


AimsChronic kidney disease (CKD) is a risk factor for left ventricular hypertrophy (LVH) and heart failure. We evaluated the effect of CKD on left ventricular (LV) remodelling among patients with mild heart failure.Methods and resultsREVERSE was a randomized, controlled trial evaluating cardiac resynchronization therapy (CRT) in patients with New York Heart Association (NYHA) class I/II heart failure. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared changes in LV function and size over the course of 12 months by CKD status using linear mixed models adjusted for demographics, co-morbidities, medications, cardiomyopathy aetiology, and CRT status. Finally, we evaluated the effect of CKD on cardiac remodelling among patients randomized to CRT on or off. CKD was associated with worsening LV function and dilation compared with the non-CKD group adjusted, 12-month β coefficients for the CKD group compared with the non-CKD referent group: LV ejection fraction (%) [-1.80, 95 confidence interval (CI)-3.36 to-0.24], LV end-systolic volume (mL) (14.16, 95 CI 3.96-24.36), LV end-diastolic volume (mL) (14.88, 95 CI 2.88-26.76), LV end-systolic diameter (cm) (0.36, 95 CI 0.12-0.48), LV end-diastolic diameter (cm) (0.24, 95 CI 0.012-0.36), mitral regurgitation () (3.12, 95 CI 0.48-5.76), and LV shape (0.036, 95 CI 0.012-0.060). In participants assigned to CRT, those without CKD had significantly greater improvements in LV structural parameters compared with the CKD group.Conclusions
In comparison with participants with normal kidney function, CKD is an independent risk factor for ventricular dysfunction and dilation. CRT improves LV function and structure to a lesser extent in patients with CKD than in those with normal kidney function.

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Available from: Cecilia Linde, Sep 03, 2014
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    • "In addition, historical values of BP readings were not available for comparison and the relatively small sample size could account for the lack of association between GLS and BP seen in this study. CKD is a unique risk factor for cardiac remodeling; studies have demonstrated that this occurs early and is significantly worse in CKD patients compared to non- CKD[30,31]. The structural changes are characterized by cardiomyocyte cell loss and hypertrophy, increased wall stress, dilatation or thinning of ventricular wall, scar formation and myocardial fibrosis which progresses to a maladaptive response and results in functional decom- pensation[32,33]. "
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    ABSTRACT: Background: Global longitudinal strain (GLS) has emerged as a superior method for detecting left ventricular (LV) systolic dysfunction compared to ejection fraction (EF) on the basis that it is less operator dependent and more reproducible. The 2-dimensional strain (2DS) method is easily measured and integrated into a standard echocardiogram. This study aimed to determine the relationship between GLS and traditional and chronic kidney disease (CKD)-related risk factors of cardiovascular disease (CVD) in patients with CKD. Methods: A cross sectional study of patients with moderate CKD stages 3 and 4 (n = 136). Clinical characteristics, anthropometric, biochemical data including markers of inflammation [C-reactive protein (CRP)], uremic toxins [indoxyl sulphate (IS), p-cresyl sulphate (PCS)], and arterial stiffness [pulse wave velocity (PWV)] were measured. Inducible ischemia was detected using exercise stress echocardiogram. GLS was determined from 3 standard apical views using 2-dimensional speckle tracking and EF was measured using Simpson's rule. Associations between GLS and traditional and CKD-related risk factors were explored using multivariate models. Results: The study population parameters included: age 59.4 ± 9.8 years, 58 % male, estimated glomerular filtration rate (eGFR) 44.4 ± 10.1 ml/min/1.73 m(2), GLS -18.3 ± 3.6 % and EF 65.8 % ± 7.8 %. This study demonstrated that GLS correlated with diabetes (r = 0.21, p = 0.01), history of heart failure (r = 0.20, p = 0.01), free IS (r = 0.24, p = 0.005) free PCS (r = 0.23, p = 0.007), body mass index (BMI) (r = 0.28, p < 0.001), and PWV (r = 0.24, p = 0.009). Following adjustment for demographic, baseline co-morbidities and laboratory parameters, GLS was independently associated with free IS, BMI and arterial stiffness (R(2) for model = .30, p < 0.0001). Conclusions: In the CKD cohort, LV systolic function assessed using GLS was associated with uremic toxins, obesity and arterial stiffness.
    Full-text · Article · Jul 2015 · BMC Nephrology
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    • "It is increasingly recognized that both a low glomerular filtration rate and increased urinary protein excretion are associated with an adverse cardiac or cardiovascular outcome [24, 25]. Both low eGFR [11, 18] and proteinuria [26] have been shown to be associated with cardiac remodeling. On the other hand, as compared with the relationship between eGFR and FGF23/α-Klotho, information seems to be limited regarding the relationship association between proteinuria (or albuminuria) and FGF23/α-Klotho. "
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    ABSTRACT: Background Expression and/or excretion of fibroblast growth factor-23 (FGF23) and its co-receptor Klotho are altered in patients with end-stage renal disease. The possibility that the FGF23/α-Klotho system mediates the aggravated cardiovascular outcome among patients with chronic kidney disease (CKD) has been suggested. We determined whether FGF23 and α-Klotho concentrations are altered among patients with reduced renal function and proteinuria. Methods Serum FGF23 and α-Klotho were measured in cardiology patients who were not undergoing chronic hemodialysis. Estimated glomerular filtration rate (eGFR) was correlated negatively with FGF23 and positively with α-Klotho. Results The correlation between FGF23 and the renal tubular maximum reabsorption rate of phosphate to the GFR (TmP/GFR) was not significant, but that between FGF23 and serum calcium or inorganic phosphate was significant among patients with an estimated GFR of less than 60 mL/min/m2. By stepwise multivariate regression analysis, eGFR was selected as significant predictor for FGF23 or α-Klotho among patients with an estimated GFR of less than 60 mL/min/m2; however, urine albumin/creatinine ratio was not selected as a predictor for FGF23 or α-Klotho irrespective of the eGFR levels. In patients with eGFR of <60 mL/min/1.73 m2, UACR was significantly associated with log(FGF23); but, this association did not remain statistically significant in a multivariate model. Conclusions Among cardiology patients with various stages of CKD, serum concentrations of FGF23 and α-Klotho were associated with renal function, but not with the extent of proteinuria.
    Full-text · Article · Sep 2014 · BMC Nephrology
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    • "Hypertensive target organ damage includes impaired renal function and left ventricular hypertrophy (LVH). Impaired renal function is an independent marker for LVH and a good predictor of morbidity and mortality in cardiovascular disease.[1],[2] In patients with chronic kidney disease (CKD), there is a significant association between decreased estimated glomerular filtration rate (eGFR) and LVH.[3] "
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    ABSTRACT: Serum cystatin C levels can be used to predict morbidity and mortality in patients with cardiovascular disease. However, the clinical relevance of serum cystatin C levels in patients with hypertensive left ventricular hypertrophy (LVH) has rarely been investigated. We designed the present study to investigate whether serum cystatin C levels are associated with cardiac structural and functional alterations in hypertensive patients. We enrolled 823 hypertensive patients and classified them into two groups: those with LVH (n = 287) and those without LVH (n = 536). All patients underwent echocardiography and serum cystatin C testing. We analyzed the relationship between serum cystatin C levels and LVH. Serum cystatin C levels were higher in hypertensive patients with LVH than in those without LVH (P < 0.05). Using linear correlation analysis, we found a positive correlation between serum cystatin C levels and interventricular septal thickness (r = 0.247, P < 0.01), posterior wall thickness (r = 0.216, P < 0.01), and left ventricular weight index (r = 0.347, P < 0.01). When analyzed by multiple linear regression, the positive correlations remained between serum cystatin C and interventricular septal thickness (β = 0.167, P < 0.05), posterior wall thickness (β = 0.187, P < 0.05), and left ventricular weight index (β = 0.245, P < 0.01). Serum cystatin C concentration is an independent marker for hypertensive LVH.
    Full-text · Article · Sep 2013 · Journal of Geriatric Cardiology
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