Relation between renal function and response to cardiac resynchronization therapy in Multicenter Automatic Defibrillator Implantation Trial--Cardiac Resynchronization Therapy (MADIT-CRT)

Background: Cardiorenal interactions have been shown to affect outcome in heart failure patients but were not related to response to cardiac resynchronization therapy (CRT).

Objective: The purpose of this study was to test our hypothesis that assessment of markers of prerenal failure may help identify mildly symptomatic HF patients with diminished effective circulating blood volume who will benefit from CRT.

Methods: The benefit of CRT with a defibrillator (CRT-D) as compared with defibrillator-only therapy in reducing the risk of HF or death was assessed by renal function parameters (including serum creatinine [SCr], blood urea nitrogen [BUN], and the ratio of BUN to SCr [BUN:SCr], dichotomized at median values and into approximate quartiles) among 1,803 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy.

Results: Multivariate analysis showed that the benefit of CRT-D was inversely related to SCr levels and directly related to BUN levels. Combined assessment of the two renal function parameters showed a significant difference in the benefit of CRT-D between patients with low (≤ 18 mg/dL, HR = 0.85, P = .28) and elevated (> 18 mg/dL, HR = 0.46, P < .001) BUN:SCr (P-value for interaction = .005). Consistently, the benefit of CRT-D was significantly increased with increasing quartiles of BUN:SCr (Q(1): HR = 1.06 [P = .79], Q(2): HR = 0.64 [P = .04], Q(3): HR = 0.47 [P < .001], Q(4): HR = 0.44 [P < .001]; P-value for trend = .005).

Conclusions: In MADIT-CRT, patients with an elevated ratio of BUN to SCr experienced a significantly greater reduction in the risk of HF or death with CRT-D therapy as compared with patients with a low ratio. These findings suggest an association between prerenal function and response to CRT.