Cardiac Resynchronization Therapy Improves Renal Function in Human Heart Failure With Reduced Glomerular Filtration Rate

doi:10.1016/j.cardfail.2008.03.009

Journal of Cardiac Failure

Volume 14, Issue 7, September 2008, Pages 539-546

https://doi.org/10.1016/j.cardfail.2008.03.009 Get rights and content

Abstract

Background

Renal dysfunction is an important independent prognostic factor in heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony, but the impact of CRT on renal function is less defined. We hypothesized that CRT would improve glomerular filtration rate as estimated by the abbreviated Modification of Diet in Renal Disease equation (eGFR).

Methods and Results

The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study evaluated CRT in HF patients with NYHA Class III-IV, ejection fraction ≤35%, and QRS ≥130 ms. Patients were evaluated before and 6 months after randomization to control (n = 225) or CRT (n = 228). Patients were categorized according to their baseline eGFR: ≥90 (category A), 60 ≤eGFR <90 (category B), and 30 ≤eGFR <60 (category C) mL/min per 1.73 m². CRT improved LV function in all categories. Compared with control, CRT increased eGFR (−2.4 ± 1.2 vs. +2.7 ± 1.2 mL/min per 1.73 m²; P = .003) and reduced blood urea nitrogen (+6.4 ± 2.4 vs. −1.1 ± 1.5 mg/mL; P = .008) in category C, whereas no differences were observed in categories A and B.

Conclusions

CRT increased eGFR and reduced blood urea nitrogen in HF patients with moderately reduced baseline eGFR. By improving cardiac function, CRT can indirectly improve renal function, underscoring the importance of cardiorenal interaction and providing another mechanism for the beneficial effects of CRT.

Section snippets

Methods

The present study is a retrospective analysis of the MIRACLE trial, which has been reported in detail previously.8, 9 Only patients with paired eGFR values at baseline and at 6 months were included in this analysis.

Results

Baseline characteristics of the 453 patients participating in the MIRACLE trial were reported previously with no significant differences between control and CRT groups.⁸ However, patients randomized to CRT in eGFR category C were more likely to be on a β-blocker at baseline (control 44% vs. CRT 63%, P = .02). Of the 448 patients who had baseline creatinine values available, 16% had a normal eGFR (category A), 40% had mildly impaired renal function (category B), and 39% had moderately decreased

Discussion

This study reports for the first time that CRT in a randomized placebo-controlled clinical trial in human HF improves eGFR and reduces BUN in patients with moderately decreased eGFR at baseline (30–59 mL/min per 173 m²). We also found that decreased baseline eGFR is associated with increased age, ischemic HF etiology, more severe mitral regurgitation, reduced blood pressure, and increased neurohumoral activation.

Although there is a large body of evidence implicating a decline in eGFR and

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Citation Excerpt :
With CRT therapy, the RV and LV are paced in a synchronized manner, improving cardiac function and reducing mitral regurgitation. In the MIRACLE study, 453 HF patients with NYHA Class III-IV, LVEF <35% and QRS >130 ms were randomized to CRT or control and results were analyzed according to baseline eGFR (the trial excluded patients with eGFR <30 ml/min per 1.73 m2).167 While CRT improved LV function in all patients regardless of eGFR, in patients with eGFR between 30 and 60 ml/min per 1.73 m2, CRT was also seen to significantly increase eGFR and reduce blood urea nitrogen levels compared with controls Despite these benefits, several studies have demonstrated that renal dysfunction is also associated with higher long-term mortality in CRT patients, once again highlighting the increased overall mortality among patients with concomitant CKD and HF.168,169
Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.
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: Supported by grants from the NIH (POI HL076611 and HL36634 (J.C.B., Jr) HL07111 (G.B. and L.C.C.-B.)), and the Mayo Foundation. The MIRACLE trial was supported by Medtronic.

: Michael R.S. Hill and Kristin M. Kruger are employed by Medtronic, Inc. William T. Abraham and Martin G. St. John Sutton are consultants for Medtronic, Inc.

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Clinical TrialCardiac Resynchronization Therapy Improves Renal Function in Human Heart Failure With Reduced Glomerular Filtration Rate

Abstract

Background

Methods and Results

Conclusions

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Int J Cardiol

J Card Fail

Mayo Clin Proc

Am Heart J

J Am Coll Cardiol

Renal function, neurohormonal activation, and survival in patients with chronic heart failure

Circulation

Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study

Circulation

Renal function as a predictor of outcome in a broad spectrum of patients with heart failure

Circulation

Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay

N Engl J Med

Cardiac resynchronization in chronic heart failure

N Engl J Med

Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure

Circulation

Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure

N Engl J Med

The effect of cardiac resynchronization on morbidity and mortality in heart failure

N Engl J Med

Cardiac resynchronization therapy: an option for inotrope-supported patients with end-stage heart failure?

Eur J Heart Fail

A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group

Ann Intern Med

Clinical Trial
Cardiac Resynchronization Therapy Improves Renal Function in Human Heart Failure With Reduced Glomerular Filtration Rate