Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation

Abstract

Background: Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure.

Methods and results: A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125-150 mg/dL, 67-85 mg/dL, 32-42 mg/dL, and 97-126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212-0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092-0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support.

Conclusions: Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support.

Keywords: cholesterol; heart failure; heart-assist devices; lipids; transplantation.

Figure 1

A to D, Trend in median lipid values over time with reference to the time of left ventricular assist device (LVAD) implantation. Total cholesterol, low-density lipoprotein (LDL), and triglyceride levels fell in the 9 mo preceding LVAD implantation. After a nadir around the time of LVAD implantation, all 4 lipid variables significantly increased in the following 9 mo of LVAD support, with the steepest gradients between the time of implantation and 3 mo post-LVAD implantation. Lipid values were assigned to time points as follows: −9 mo, −270±30 d (−300 to −240); −6 mo, −180±30 d (−210 to −150); −3 mo: −90±30 d (−120 to −60); implant date: 0±30 d (−30 to +30); 3 mo: 90±30 d (60–120); 6 mo: 180±30 d (150–210); and 9 mo: 270±30 d (240–300). *P≤0.05; **P≤0.01; ***P≤0.001.

Figure 2

A to D, Median lipid values at 3 mo post implantation in survivors vs nonsurvivors of left ventricular assist device (LVAD) support. The values displayed are the median levels for each of the 4 lipid variables at 3 mo (±30 d) post-LVAD implantation. Individuals who survived LVAD support to the time of cardiac transplantation, LVAD explantation, or administrative censoring, had a significantly higher median total cholesterol value than individuals who died on LVAD support. There was no significant association between survival status and median low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglyceride levels. *P≤0.05; **P≤0.01; ***P≤0.001.

Figure 3

A to D, Kaplan–Meier plots for unadjusted survival by degree of change in lipids from left ventricular assist device (LVAD) implantation to 3 mo post implantation (above/below median change). Incorporation of time-to-event information shows superior survival on LVAD support for individuals whose change in total cholesterol or triglyceride levels were above the median at 3 mo (±30 d) post-LVAD implantation. There was no significant association between the low-density lipoprotein (LDL) or high-density lipoprotein (HDL) level at 3 months post-LVAD implantation and survival on LVAD support.

Figure 4

Spline function curve for the impact of cholesterol level at 3 mo after left ventricular assist device (LVAD) implantation on mortality during LVAD support. The hazard of mortality reaches a lower threshold around a total cholesterol level of 130 mg/dL at 3 mo post-LVAD implantation. The nadir for the hazard of mortality is around 170 mg/dL. The spline curve adjusted for age, ischemic heart failure cause, ejection fraction, bridge-to-transplantation strategy, and baseline cholesterol is displayed.

Figure 5

A hypothesis for metabolic recovery after left ventricular assist device (LVAD) implantation in advanced heart failure. LDL indicates low-density lipoprotein.