CareDx Announces Publication of New SHORE Study Demonstrating the Prognostic Power of HeartCare® for Heart Transplant Recipients in the Journal of Heart and Lung Transplantation
CareDx, Inc. (Nasdaq: CDNA), a global leader in precision medicine dedicated to improving outcomes for transplant patients and the clinicians who care for them, announced the publication of the third manuscript from the Surveillance HeartCare Outcomes Registry (SHORE) in the Journal of Heart and Lung Transplantation (JHLT). This manuscript, titled “Multimodal Molecular Testing Provides Prognostic Value for Heart Transplant Recipients,” provides compelling new evidence supporting the pivotal role of HeartCare®—CareDx’s multimodal molecular surveillance solution—in predicting adverse outcomes following heart transplantation.
The SHORE registry is one of the most comprehensive, real-world datasets evaluating outcomes in heart transplant recipients monitored with molecular diagnostics. The registry was designed to assess how noninvasive biomarker tools—specifically AlloMap®, a gene expression profiling test, and AlloSure® Heart, a donor-derived cell-free DNA (dd-cfDNA) assay—can reveal early signs of graft injury, rejection risk, and long-term complications. The newly published analysis marks an important step forward in understanding the clinical value of combining these assays within the HeartCare platform.
Study Scope and Purpose
The third SHORE manuscript analyzed data from a large, diverse cohort comprising 1,934 heart transplant recipients treated across 59 transplant centers in the United States. These patients were followed longitudinally, enabling investigators to track how molecular signals from HeartCare correlated with subsequent clinical events, including rejection, graft dysfunction, and cardiovascular mortality.
One of the study’s central objectives was to determine whether HeartCare could detect risk that standard histological biopsy might miss. Endomyocardial biopsy (EMB) has long been considered the gold standard for evaluating rejection, yet EMB has important limitations, including sampling error, inter-reader variability, and inability to detect subtle or evolving molecular injury. The SHORE analysis provides robust evidence that a multimodal molecular approach may offer prognostic insight above and beyond biopsy alone.
Major Outcomes and Prognostic Insights
Across the entire SHORE population, investigators found that patients who exhibited positive HeartCare results—meaning elevations in both AlloMap gene expression and AlloSure Heart dd-cfDNA—were at substantially greater risk for adverse clinical events. Importantly, these signals were prognostically meaningful even when biopsy results appeared normal, underscoring the unique and independent value of molecular diagnostics.
Dr. Kiran Khush, Professor of Medicine at Stanford University and the study’s corresponding author, emphasized the clinical implications of these findings. She noted:
“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. With this prognostic information, clinicians can closely monitor patients who most need it, potentially improving their outcomes.”
Dr. Khush’s statement reflects a growing shift within the transplant community toward integrating molecular biomarkers as routine components of post-transplant management, particularly in high-risk periods.
Key Findings From the SHORE Manuscript
The study presents several important insights:
1. Early Post-Transplant HeartCare Positivity Strongly Predicts Adverse Outcomes
Between 2 and 6 months post-transplant, patients who had a positive HeartCare result were found to have nearly double the 1-year cumulative incidence of graft dysfunction and cardiovascular death compared with other molecular result categories
(15.5% compared with 8.5% or lower, p = 0.009).
This is particularly meaningful because the early post-transplant period is a time when subtle graft injury may not be easily captured by biopsy alone. The study suggests that HeartCare may help physicians identify patients who would benefit from more intensive surveillance or therapeutic intervention.
2. Prognostic Value Independent of Biopsy Findings
A crucial takeaway from the analysis is that the heightened risk associated with positive HeartCare results persisted even in patients whose biopsies showed no histological evidence of rejection.
This finding reinforces the growing recognition that biopsy alone may be insufficient to detect all forms of graft injury or early immune activation. Molecular signals may precede histological changes, offering a valuable early-warning system for clinicians.
3. Elevated Risk Across the Long-Term Post-Transplant Period
The SHORE data also demonstrated that a positive HeartCare result at any timepoint between 2 months and 5 years post-transplant was linked to a threefold increase in the 30-day risk of graft dysfunction or cardiovascular death. This short-term, event-proximal relationship indicates that molecular abnormalities identified by HeartCare are not merely theoretical markers—they correlate directly with clinically meaningful outcomes.
4. Added Risk Signal Even in the Setting of Acute Cellular Rejection
Among patients with biopsy-confirmed acute cellular rejection (ACR), molecular testing provided additional granularity. Those who were also HeartCare-positive were found to have significantly higher risk of subsequent graft dysfunction or cardiovascular death, compared with those exhibiting other molecular result patterns.
This result challenges the assumption that biopsy results alone can fully characterize the severity or trajectory of rejection-related injury. Even in confirmed ACR, HeartCare offered actionable prognostic information.
A Paradigm Shift in Post-Transplant Surveillance
Dr. Jeff Teuteberg, Chief Medical Officer of CareDx, emphasized the broader clinical significance of these findings:
“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. 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 remarks highlight how SHORE strengthens the case for a new era in transplant surveillance—one where multimodal molecular assessment may guide earlier intervention, prevent graft injury from progressing, and ultimately improve long-term survival.
Implications for Clinical Practice
The findings from the SHORE manuscript support several important shifts in patient management:
- Incorporation of molecular testing as a routine complement to biopsy, enabling a more comprehensive assessment of graft health.
- Identification of high-risk patients earlier, particularly in the vulnerable early post-transplant period.
- Potential for tailored immunosuppression strategies, guided by the molecular profile rather than relying exclusively on histology.
- Opportunity to reduce unnecessary biopsies in low-risk patients, sparing them from invasive procedures.
- Foundation for future prospective trials, including studies designed to test whether modifying therapy based on molecular abnormalities improves outcomes.
HeartCare’s multimodal design—integrating cellular gene expression (AlloMap) with dd-cfDNA injury signals (AlloSure Heart)—allows clinicians to interpret graft health through multiple biological pathways. The SHORE results confirm that this combined approach yields a more nuanced and predictive understanding of post-transplant risk.
About the SHORE Registry
The Surveillance HeartCare Outcomes Registry was established to evaluate the real-world effectiveness of molecular monitoring in heart transplantation. With data collected from nearly sixty centers, SHORE is one of the largest longitudinal cohorts ever analyzed for molecular diagnostics in heart transplantation. The publication of the third manuscript adds to a growing body of evidence demonstrating the clinical utility of noninvasive surveillance tools.
Accessing the Full Publication
The full manuscript is available through the Journal of Heart and Lung Transplantation:
https://www.jhltonline.org/article/S1053-2498(25)02400-3/fulltext
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