CareDx Announces Publication of Third SHORE Study in JHLT, Demonstrating the Strong Prognostic Value of HeartCare for Heart Transplant Recipients
CareDx, Inc., a pioneer in precision medicine dedicated to improving outcomes for organ transplant patients, has announced the publication of the third manuscript from its ongoing Surveillance HeartCare Outcomes Registry (SHORE). This new study, featured in the Journal of Heart and Lung Transplantation (JHLT), further strengthens evidence supporting the clinical power of HeartCare®, a multimodal molecular testing solution designed to guide post-transplant management and decision-making.
The newly published manuscript, titled “Multimodal Molecular Testing Provides Prognostic Value for Heart Transplant Recipients,” represents a major advancement in the understanding of how molecular diagnostics can reveal hidden threats to cardiac graft health—often before they are detectable through traditional biopsy methods. By integrating results from both AlloMap® (a gene expression profiling test) and AlloSure® Heart (a donor‐derived cell-free DNA test), HeartCare provides clinicians with a comprehensive and sensitive tool for monitoring transplant health at multiple biological levels.
A Study of Unprecedented Scale in Heart Transplant Molecular Monitoring
This third SHORE analysis included a robust cohort of 1,934 heart transplant recipients across 59 transplant centers, making it one of the most extensive real-world evaluations of multimodal molecular testing in the field of cardiac transplantation. The longitudinal nature of the registry enabled researchers to examine not only short-term outcomes but also how molecular markers correlate with long-term risks such as graft dysfunction, cardiovascular death, and rejection-related complications.
One of the most significant findings was that positive HeartCare results were predictive of adverse events even when endomyocardial biopsy findings appeared normal. This underscores the increasing recognition that traditional histology, while valuable, may not detect early molecular-level injury or evolving graft instability. HeartCare’s ability to stratify a patient’s risk even in ambiguous or “normal-appearing” clinical scenarios highlights its value as a complementary and highly informative tool.
Expert Perspectives on the Clinical Importance of the Findings
Dr. Kiran Khush, Professor of Medicine at Stanford University and corresponding author of the study, emphasized how the findings redefine early risk detection in heart transplantation.
“This analysis from SHORE demonstrated that positive HeartCare results—when both AlloMap and AlloSure are elevated—pinpoint the heart transplant recipients at highest risk for graft dysfunction and cardiovascular death,” said Dr. Khush.
“With this prognostic information, clinicians can closely monitor patients who most need it, potentially improving their outcomes.”
Dr. Khush’s remarks underscore the clinical utility of using multimodal biomarkers as early warning signals, particularly for patients whose biopsies may not yet show visible rejection patterns but who are nonetheless at heightened risk.
Dr. Jeff Teuteberg, Chief Medical Officer at CareDx, offered additional insights into how these SHORE findings could help shift long-standing paradigms in heart transplant surveillance:
“These SHORE analyses challenge the paradigm of the biopsy as the gold standard for assessing graft injury, showing that HeartCare’s molecular insights can identify risk that histology alone may miss,” said Dr. Teuteberg.
“This study empowers clinicians to deliver more personalized care and establishes the scientific rationale for an interventional study to test the impact of treating patients with abnormal HeartCare results despite having a normal biopsy.”
Dr. Teuteberg’s comments reinforce a growing body of clinical belief that multimodal, noninvasive testing will be an increasingly important part of individualized transplant care in the future.
Key Findings From the SHORE Analysis
The SHORE registry results provide several compelling insights, each highlighting how molecular monitoring enhances risk assessment throughout the critical months and years following a heart transplant.
1. Molecular positivity between 2–6 months post-transplant signals elevated future risk
Patients who presented with positive HeartCare results (both AlloMap and AlloSure Heart elevated) during the vulnerable early post-transplant period—specifically months 2 through 6—showed a nearly twofold higher cumulative incidence of graft dysfunction and cardiovascular death in the following year.
- 15.5% cumulative incidence for HeartCare-positive patients
- 8.5% or lower incidence for all other comparison groups
- Statistical significance: p = 0.009
These findings reinforce the importance of comprehensive surveillance during the first several months post-transplant, a time when subtle molecular shifts may precede clinically detectable complications.
2. Elevated risk persists even when biopsies appear normal
One of the most notable discoveries is that positive HeartCare results predict adverse outcomes independently of biopsy findings.
Even in patients who showed no histological evidence of rejection, molecular signals revealed through AlloMap and AlloSure were highly predictive of subsequent complications. This suggests that the biopsy—long considered the gold standard—may miss early molecular changes that foreshadow injury or graft instability.
HeartCare provides additional layers of insight that can help clinicians identify concerning patterns earlier and more accurately.
3. Positive HeartCare results predict near-term complications up to 5 years post-transplant
The study examined HeartCare results across a long post-transplant window (from 2 months up to 5 years). Regardless of when positivity occurred, a positive HeartCare result at any time was associated with a threefold increase in the 30-day risk of graft dysfunction or cardiovascular death.
This demonstrates that HeartCare provides actionable prognostic information not only in the early post-transplant phase, but also during long-term follow-up when risks can become more unpredictable.
4. Molecular risk signals remain powerful even in the context of acute cellular rejection
Another important finding is that even among patients diagnosed with acute cellular rejection (ACR), those with positive HeartCare results faced significantly higher risk of subsequent adverse outcomes compared to those with other molecular result profiles.
This suggests that HeartCare can help differentiate risk levels within subgroups already known to be vulnerable, enabling clinicians to identify which ACR patients require more aggressive monitoring or treatment adjustments.
Implications for the Future of Heart Transplant Care
The findings from this third SHORE manuscript contribute to a growing body of evidence supporting the integration of molecular diagnostics into routine transplant surveillance. Historically, heart transplant monitoring has relied heavily on biopsies, which are invasive, resource-intensive, and sometimes limited in their ability to detect early injury.
By contrast, HeartCare’s multimodal testing strategy provides:
- A noninvasive assessment of immune activity and graft injury
- Earlier detection of risks that biopsies may not reveal
- Improved ability to stratify patient risk over time
- A tool for guiding more personalized clinical management
The publication of this study in a leading transplant journal underscores its importance and the potential it holds for reshaping clinical standards.
As Dr. Teuteberg noted, the SHORE findings lay a foundation for future interventional research aimed at determining whether early therapeutic action—guided by molecular insights—can improve long-term outcomes for heart transplant patients.
