Invasive coronary angiography is the reference standard for diagnosing coronary artery disease, yet assessment is subjective, and existing artificial-intelligence tools typically assess stenosis in individual frames or videos and do not integrate the full multiview angiographic study. Here we show that DeepCORO-CLIP, trained on 203,808 angiographic videos and reports from 28,117 patients, interprets whole multiple-video angiograms at once. It detects obstructive stenoses (≥70%), with an area under the receiver operating characteristic curve (AUROC) of 0.89 internally and externally, and identifies chronic total occlusion (AUROC = 0.90 to 0.95), intra-coronary thrombus and calcification (AUROC = 0.90 to 0.91). It also predicts 1-year cardiovascular events (AUROC = 0.79, 95% CI of 0.74 to 0.84, versus 0.65 for a model derived using clinical variables) and left ventricular ejection fraction (mean absolute error 7.3% versus 8.8% for a previous model), both achieved using coronary angiography alone. In a blinded review of 365 evaluations across 288 angiograms, its reports were clinically usable in 76% of evaluations versus 88% for cardiologists, with comparable false positives (17% versus 14%, P = 0.38); residual missed stenoses reflected an adjustable threshold rather than an absent signal.

Chronic immune activation contributes to cardiometabolic disease and has most often been attributed to soluble mediators or changes in individual immune-cell subsets. A complementary dimension of immune organization is captured by direct physical interactions between immune cells, detected in blood or dissociated samples. While most dual-lineage flow-cytometric events should still be excluded as technical doublets, a validated subset represents true cell-cell conjugates (i.e., physically interacting immune cells rather than antibody-antigen complexes). The evidence base, however, is uneven as platelet-leukocyte aggregates are well-established biomarkers of platelet activation and thromboinflammation, while circulating non-platelet immune cell-cell complexes, particularly T cell-monocyte complexes, remain an emerging field supported by relatively few primary studies. Across acute infection and vaccination, these complexes appear regulated and may reflect coordinated immune activation. In chronic inflammatory states, including HIV and metabolic dysfunction, persistent complexes have been associated with inflammation and cardiometabolic risk, although mechanistic and causal data remain limited. Here, we review the current evidence for circulating immune cell complexes, distinguish established platelet-containing aggregates from the nascent literature on other immune-cell pairings, discuss candidate mechanisms that may support their formation and persistence, outline methodological requirements for their study, and consider their potential as biomarkers and therapeutic-response tools in cardiometabolic disease.

Right ventricular failure (RVF) independently predicts mortality in heart failure, yet its pathophysiology is poorly understood. Here we present a multi-modal atlas of human right ventricular pressure loading and failure, including bulk (n = 142), single-nucleus (n = 11) and Xenium spatial (n = 9) transcriptomics in adults, plus pediatric (n = 14) and mouse pulmonary artery banding cohorts. Subclustering resolved 34 cell subtypes across 12 lineages along a two-phase trajectory. Phase 1 (non-failing to pressure-loaded) accounts for most of the transcriptional change detectable by bulk and single-nucleus RNA sequencing and is marked by loss of resident macrophage identity, fibroblast activation, endothelial expansion and erosion of tissue-protective programs. Phase 2 (pressure-loaded to RVF) produces little change in bulk RNA sequencing but is resolved by spatial transcriptomics, engaging multi-lineage fibrotic, endothelial-activation and cardiomyocyte-reactivation programs, with a gain of extracellular matrix (collagen, laminin, thrombospondin) signaling over a stable cell contact adhesion baseline. Mitochondrial respirometry revealed respiratory dysfunction in adult and mouse RVF but not pediatric RVF. Multi-lineage remodeling of the cardiac microenvironment emerges as the central molecular program of RVF, meriting further study as possible disease-modifying targets.

The age-related decline in growth hormone (GH) secretion, termed the somatopause, parallels the structural and functional deterioration of the aging heart. How this endocrine withdrawal translates into myocardial failure at the molecular level remains incompletely mapped. GH/insulin-like growth factor 1 (IGF-1) signaling acts via PI3K/Akt/mTOR and Ras/MAPK/c-Myc cascades on four processes central to cardiac aging: Akt-dependent nuclear retention of telomerase reverse transcriptase (TERT), established primarily in non-cardiomyocyte models; PGC-1α-driven mitochondrial biogenesis; suppression of the p53/p16INK4a senescence program; and metabolic-epigenetic regulation of cell-cycle competence via α-ketoglutarate/KDM5 and JMJD3 chromatin gating. In mouse cardiomyocytes, positive transcription elongation factor b (P-TEFb) is rate-limiting for Myc-driven proliferation, plausibly explaining why adult cardiomyocytes retain latent cell-cycle machinery yet rarely divide. A candidate GHRHR-HIF-1α axis, presently supported by preprint evidence, is examined as an emerging hypothesis for cell-type-selective cardioprotection independent of systemic GH. We integrate these strands along a single tractable axis: IGF-1/Akt/TERT/p53/PGC-1α with metabolic-epigenetic modulation. The 2025 Marra trial (NCT03775993; 64 randomized, 45 completers; surrogate and functional endpoints not powered for clinical events) reports that physiological GH restoration improves peak VO2 (+3.1 vs -1.8 mL/kg/min, P<0.01), NYHA class, and quality of life in heart failure with confirmed GH deficiency. A meta-analysis of 25 studies quantifies the U-shaped IGF-1-heart failure relationship, with the HF-versus-control IGF-1 difference derived from six of those studies. Plasma proteomic organ-aging signatures show accelerated cardiac aging is associated with 2.5-fold heart-failure risk. We present a hypothesis-generating framework identifying GH/IGF-1 axis restoration as a candidate determinant of heart-failure progression, warranting event-driven confirmation.