Researchers from Harvard Medical School in collaboration with the Max Delbrück Center for Molecular Medicine in Germany have uncovered notable differences in how heart cells activate genes across several forms of cardiomyopathy that can culminate in heart failure. The findings, published in Science, illuminate why some patients with cardiomyopathy deteriorate while others stay stable, and point toward more precise care paths for North American patients, including those in Canada and the United States.
The team studied heart tissue from 61 individuals diagnosed with heart failure due to various cardiomyopathies and 18 individuals who did not show structural heart disease at the time of analysis. Using advanced single-cell RNA sequencing, the researchers measured gene activity across ten distinct heart cell types. This fine-grained view reveals how each cell population contributes to disease progression and how gene programs shift as heart failure develops.
To interpret these complex data, the investigators employed machine learning to detect patterns in gene expression associated with different cardiomyopathy types and with heart failure status. The approach highlighted a common expansion of endothelial and immune cell populations in all patients, indicating widespread vascular and inflammatory involvement in disease. In contrast, the number of connective tissue cells, including fibroblasts responsible for scar formation, did not change in quantity; rather, their gene activity altered dramatically in those with heart failure. These shifts in transcriptional programs suggest that heart failure emerges not merely from cell loss, but from widespread reprogramming of cellular behavior across the heart’s cellular ecosystem.
The study emphasizes that many forms of cardiomyopathy capable of hindering the heart’s pumping ability—such as dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM)—can progress toward heart failure. What’s critical from a clinical perspective is that the specific cardiomyopathy type has often not been a determining factor in standard heart-failure treatment. The researchers argue that recognizing distinct gene-activity profiles for each cardiomyopathy type could enable personalized therapy and more efficient patient screening through affordable genotyping. This precision-focused approach holds promise for improving outcomes in North America, where cardiovascular disease remains a leading cause of illness and disability. It may also streamline screening and risk stratification, making advanced genetic insights accessible to a broader patient population in Canada and the United States. The integration of gene-expression data with clinical care could shape future guidelines on how cardiomyopathy is diagnosed, monitored, and treated in routine practice, potentially guiding early interventions and targeted therapies tailored to a patient’s specific disease subtype. The work adds to a growing body of evidence that cell-type–specific genetic activity matters for heart disease and underscores the value of cross-institutional collaborations for translating molecular findings into practical care strategies. The study’s authors anticipate that these insights will spur the development of genotype-informed treatment plans and cost-effective screening tools that can be adopted widely across North America and beyond. The work also opens avenues for exploring how lifestyle, comorbidities, and environmental factors might interact with gene-activation patterns in different cardiomyopathies, shaping individual risk and response to treatment. Continued research in diverse patient populations will be essential to confirm these findings and to translate them into clinical practice that benefits patients in Canada, the United States, and elsewhere. The insights from this study illustrate how modern genomics and machine learning can converge to reveal the cellular choreography behind heart disease and guide more personalized and proactive care for those facing cardiomyopathy. Attribution: Harvard Medical School and the Max Delbrück Center for Molecular Medicine, Science publications and collaborating institutions.