Heart Allograft Rejection: Detection with Breath Alkanes in Low Level - HARDBALL


Assessment of the accuracy of a breath analyzer for the detection of heart transplant rejection compared with biopsy.

Study Design

Patients Enrolled: 539

Drug/Procedures Used:

In the Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels (HARDBALL) study, 539 heart transplant patients scheduled for endomyocardial biopsy to detect rejection were evaluated using a breath analyzer and results were compared to those of biopsy. Breath analysis was also performed on an equal number of healthy volunteers. The device analyzes breath samples and identifies the presence or absence of breath methylated alkanes identified with mass spectography to be markers for rejection, which are the C4 to C20 alkanes. Nine of these organic volatile compounds have been identified as being associated with grade 3 rejection.

Principal Findings:

Researchers found that breath analysis was essentially identical to biopsy in ability to determine lack of rejection (negative predictive values of 97.3 and 97.5 respectively). Breath alkane measurements had a lower positive predictive value and were less specific than biopsy in determining the presence of rejection.


The negative predictive value in determining lack of rejection was nearly the same for breath analysis and biopsy. If all heart transplant patients underwent breath analysis prior to endomyocardial biopsy, those with negative breath tests might have little to gain by biopsy results, due to the high negative predictive power of the test. Therefore, it could be speculated that the number of endomyocardial biopsy procedures could be reduced by up to 41% of the number now performed if the diagnostic accuracy of the test is confirmed.


Phillips M, Boehmer JP, Cataneo RN, et al. Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study). J Heart Lung Transplant. 2004 Jun;23(6):701-8.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant

Keywords: Healthy Volunteers, Breath Tests, Graft Rejection, Biopsy, Allografts, Heart Failure, Heart Transplantation

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