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J Heart Lung Transplant. 2019 Jun;38(6):611-618. doi: 10.1016/j.healun.2019.01.006. Epub 2019 Jan 7.

Infectious complications after heart transplantation in patients screened with gene expression profiling.

Author information

1
Section of Heart Failure, Cardiac Transplant, and Mechanical Circulatory Support, Department of Medicine, Stanford University, Stanford, California, USA; Ted Rogers Centre of Excellence for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
2
Division of Infectious Disease, Department of Medicine, Stanford University, Stanford, California, USA.
3
Ted Rogers Centre of Excellence for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
4
Section of Heart Failure, Cardiac Transplant, and Mechanical Circulatory Support, Department of Medicine, Stanford University, Stanford, California, USA.
5
Department of Medicine, Division of Infectious Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada.
6
CareDx, Inc., Brisbane, California, USA.
7
department of Medicine, West Virginia University, Morgantown, West Virginia, USA.
8
Section of Heart Failure, Cardiac Transplant, and Mechanical Circulatory Support, Department of Medicine, Stanford University, Stanford, California, USA. Electronic address: jeff.teuteberg@stanford.edu.

Abstract

BACKGROUND:

The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection.

METHODS:

The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp.

RESULTS:

The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp.

CONCLUSIONS:

In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp.

KEYWORDS:

AlloMap; cytomegalovirus; heart transplantation; immunosuppression; infectious episode; survival

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