BioSync: Transformer-Based Cross-Modal Fusion for a Multimodal Physiological Digital Biomarker

Cardiovascular disease remains the leading cause of global mortality, yet scalable cardiac monitoring is hindered by the gap between diagnostic-rich ECG and ubiquitous wearable PPG. Bridging this gap requires representations that are compact, transferable across modalities and devices, and deployable without task-specific retraining. Here we introduce biosignal fingerprints: compact latent representations of cardiovascular state derived from a cross-modal foundation model, the Multi-modal Masked Autoencoder (M2AE), trained on over 3.4 million paired ECG and PPG signals. M2AE integrates modality-specific encoders with a shared bottleneck and dual decoders, jointly optimized using reconstruction and cross-modal contrastive objectives, yielding generalizable fingerprints that retain intra- and inter-modality features. Like a biometric fingerprint, these representations uniquely encode an individual's cardiovascular state in a modality-agnostic, privacy-preserving form reusable across clinical tasks without exposing raw waveform data or requiring model retraining. Across 7 downstream tasks, spanning cross-modal reconstruction, cardiovascular disease classification, hypertension detection, mortality prediction, and demographic inference, biosignal fingerprints achieve competitive or superior performance compared to leading domain-specialist foundation models in frozen settings, including an AUROC of 0.974 for five-class CVD classification and 0.877 for hypertension detection, with a maximum improvement of 27.7% in AUROC across 5 classification tasks. Critically, strong performance is maintained with only a single modality, enabling deployment in resource-constrained, single-sensor environments typical of real-world wearable monitoring, with direct implications for continuous cardiovascular monitoring across clinical and consumer health settings.

Electrocardiography (ECG), photoplethysmography (PPG), and phonocardiography (PCG) provide complementary views of the same cardiac cycle, yet existing cardiac foundation models are trained for a single sensing modality, leaving the shared physiology across sensors unexploited. We introduce CardioState-JEPA, a cardiac foundation model to learn a single shared representation jointly across ECG, PPG, and PCG, built on a physiology-aware joint-embedding predictive architecture. The model maps heterogeneous waveforms into a common token space, processes them with a single shared Transformer encoder, and learns by predicting masked latent cardiac states, placing the pretraining target on shared physiology rather than sensor-specific waveform appearance. To handle the temporal offsets between electrical, mechanical, and hemodynamic events, cross-modal prediction uses a learned delay aligner that matches signals at the corresponding cardiac time. Because synchronized multi-sensor recordings are scarce, CardioState-JEPA first learns within-modality structure from abundant unimodal data and then uses paired data to align modalities in latent cardiac time. Evaluated as a frozen encoder across 25 downstream tasks spanning ECG, PPG, and PCG, our encoder improves average PPG classification by 8.2 AUROC points, PCG murmur detection by 18.8 AUROC points, and ECG classification by 15.5 AUROC points over the best self-supervised signal baseline and matches or exceeds cardiac models trained with privileged clinical text or supervised labels on several ECG benchmarks. These results establish that heterogeneous cardiac signals can mutually supervise a single foundation model of cardiac physiology.

Cardiovascular diagnosis rests on integrating complementary modalities, like ECG, echocardiography, chest radiographs, and clinical variables, each capturing distinct but correlated aspects of cardiac physiology. Yet most medical foundation models remain modality-specific, combining modalities only for finetuning or post-training. This discards the cross-modal evidence clinicians naturally integrate and ignores the structure within each modality. We introduce Latent-Attention Masked Autoencoders (LAMAE), a multimodal, structure-aware masked autoencoder that jointly learns patient-level representations during self-supervised pretraining. Rather than fusing modalities post hoc, LAMAE exchanges information directly in the latent space through a shared latent-attention module operating over a study-view-entity hierarchy, enabling aggregation of variable observations and graceful handling of missing modalities. Pretrained on over 1.2 million MIMIC-IV hospital stays, LAMAE outperforms modality-specific pretraining and strong contrastive and vision-language baselines across multimodal hospital-stay tasks, such as in-hospital mortality, ICD-10 and DRG coding, and length of stay, while remaining competitive on unimodal tasks. These gains persist even when only a single modality is available at test time, showing that modeling both intra- and inter-modal structure yields more robust, transferable representations.