Cardiovascular magnetic resonance measurements identified a hemodynamic pattern associated with death or heart-transplant referral or listing in people with Fontan circulation, according to a retrospective study of 182 patients followed at a moderate-altitude center. Patients who later experienced the composite outcome had a lower superior vena cava flow index than those who did not. In time-to-event analysis, each 0.1-liter-per-minute-per-square-meter increase in the indexed flow was associated with a 30% lower hazard of the outcome.

The association remained in an exploratory model that also included ventricular ejection fraction, but the researchers said the estimate requires prospective, multicenter validation before clinical application. The cohort comprised people who had undergone Fontan palliation between 1999 and 2021 at a tertiary institution approximately 5,118 feet above sea level. Fontan circulation passively directs systemic venous blood into the pulmonary arteries without the support of a sub-pulmonary ventricle.

Eligible participants had a clinically indicated CMR examination at least five years after Fontan completion, a threshold selected to match the center’s routine surveillance practice. For patients with multiple examinations, investigators used the last CMR obtained before an outcome or censoring. Most participants, 173 of 182, or 95%, had an extracardiac conduit Fontan circulation, and 76, or 42%, underwent a Damus–Kaye–Stansel anastomosis.

At CMR, the median body surface area was 1.43 square meters, with an interquartile range of 1.16 to 1.69 square meters. The median age at Fontan completion was 3.2 years, and the median interval between surgery and imaging was 10.9 years. Median follow-up after CMR was 4.7 years, while participants’ median home elevation was 5,221 feet above sea level.

Hypoplastic left heart syndrome was the most common underlying diagnosis, accounting for 35% of the cohort, followed by tricuspid atresia at 30%. The systemic ventricle was left-dominant in 53% and right-dominant in 47%. Magnetic resonance examinations were performed on 1.5- or 3.0-tesla scanners, with cine imaging used to assess ventricular function and phase-contrast sequences used to measure blood flow.

The primary endpoint combined death with referral or listing for heart transplantation. Fourteen patients, or 7.7% of the cohort, met that endpoint during follow-up: two died and 12 were referred or listed for transplantation. Among patients who experienced the outcome, the median time from CMR to the first qualifying event was 1.2 years, with an interquartile range of 0.5 to 2.5 years.

The median superior vena cava flow index was 0.54 liters per minute per square meter among patients with the primary outcome, compared with 0.82 liters per minute per square meter among those without it; the difference was statistically significant, with a p-value of 0.011. The superior vena cava-to-ascending-aorta flow ratio was also lower in the event group, with medians of 0.22 and 0.30, respectively. Several other CMR flow measures did not differ significantly between patients with and without the primary outcome.

These included flow indices in the ascending aorta, right pulmonary artery, left pulmonary artery and inferior vena cava, as well as calculated systemic-to-pulmonary collateral flow. Receiver operating characteristic analysis indicated that superior vena cava flow index discriminated between patients who met the endpoint and those who did not with an area under the curve of 0.74 and a 95% confidence interval of 0.56 to 0.92. A data-derived threshold of 0.66 liters per minute per square meter, selected using the Youden index, yielded 70% sensitivity and 75% specificity.

Kaplan–Meier curves showed significantly poorer event-free survival among patients below that threshold. Because the threshold and discrimination measures came from the same cohort, they are exploratory rather than externally validated clinical cutoffs. Univariable Cox proportional hazards regression found a hazard ratio of 0.70 for each 0.1-liter-per-minute-per-square-meter increase in superior vena cava flow index, with a 95% confidence interval of 0.50 to 0.92 and a p-value of 0.008.

Right-dominant ventricular morphology was also associated with a higher hazard than left-ventricular dominance, with a hazard ratio of 3.21, a 95% confidence interval of 1.00 to 10.29 and a p-value of 0.049. The investigators constructed a two-variable Cox model containing superior vena cava flow index and ejection fraction. Each one-percentage-point increase in ejection fraction was associated with an adjusted hazard ratio of 0.92, with a 95% confidence interval of 0.86 to 0.97.

Because only 14 primary events occurred, the multivariable analysis was deliberately restricted and was intended to test whether the flow association persisted beyond ventricular function rather than develop a full prediction model. Internal bootstrap analysis using 2,500 resamples produced a median hazard ratio of 0.71 for superior vena cava flow index and 0.92 for ejection fraction, close to the original adjusted estimates. Collinearity between the two variables was negligible, with a Spearman absolute correlation below 0.1, an R-squared value of 0.008 and a variance inflation factor of 1.01.

Tests did not indicate violation of the proportional-hazards assumption. Ventricular measures also differed according to morphology: in the right-dominant subgroup, patients with events had larger indexed ventricular volumes and lower ejection fraction than those without events, whereas comparable differences were not statistically significant in the smaller left-dominant event subgroup. The study does not establish why lower superior vena cava flow was associated with poorer outcomes.

One proposed explanation is that chronic hypobaric exposure at moderate altitude promotes pulmonary vasoconstriction and raises pulmonary vascular resistance, potentially restricting passive flow through the Fontan pathway. However, pulmonary vascular resistance was not directly measured, and the cohort included no sea-level comparator, so the study cannot determine whether altitude caused the observed hemodynamic pattern. Other possible contributors include anatomical differences in the superior vena cava, systemic venovenous collateral vessels that divert blood around the pulmonary vascular bed, and differences in preload or single-ventricle filling.

The findings therefore associate reduced indexed flow with an unfavorable hemodynamic state rather than demonstrate a specific underlying mechanism. Important limitations constrain the results. The retrospective, single-center design creates the possibility of selection bias, and clinically performed CMR examinations were not acquired at standardized surveillance intervals.

Selecting the last scan before an outcome or censoring may introduce reverse-causation bias because patients approaching clinical deterioration could have been imaged nearer the event. Clinically relevant potential confounders—including functional class, cardiopulmonary exercise capacity, resting oxygen saturation, natriuretic peptide levels, catheterization-derived Fontan pressure and pulmonary vascular resistance, pulmonary vasodilator therapy, arrhythmia burden and the severity of liver disease—were unavailable or not incorporated. The small number of events also leaves the multivariable estimates vulnerable to overfitting despite the deliberately parsimonious model and bootstrap resampling.

Furthermore, the predominance of fenestrated extracardiac conduit Fontan circulation limits generalizability to other surgical configurations. The results position superior vena cava flow index as a candidate prognostic marker that may complement ventricular size and ejection fraction in longitudinal assessment of Fontan circulation, but they do not establish a clinical measurement rule or treatment strategy. Prospective, multicenter studies comparing cohorts across elevations would be needed to test the temporal relationship, determine whether altitude modifies the association, and establish external validity.

The authors also identified four-dimensional flow CMR as a possible tool for characterizing three-dimensional flow patterns and energy loss within the Fontan pathway. Further work could compare imaging signatures with exercise physiology, biomarkers of end-organ dysfunction and pulmonary vascular imaging. Until those studies are completed, the association between reduced superior vena cava flow and adverse outcomes should be regarded as an exploratory finding that requires independent validation.

Subject of Research: Association between CMR-derived blood flow and adverse outcomes in people with Fontan circulation

Article Title: Cardiovascular magnetic resonance–derived hemodynamics predict adverse outcomes after Fontan palliation

Article References: Platnick, C., Frank, B., Romanowicz, J., Gonzalez De Alba, C., Chase, M., Umer, A., Chaudhuri, N. R., Awori, J., Chauhan, D., Mascio, C. E., Udassi, J. P., & Hedjazi Moghari, M. (2026). Cardiovascular magnetic resonance–derived hemodynamics predict adverse outcomes after Fontan palliation. Frontiers in Cardiovascular Medicine, 13, Article 1937933. https://doi.org/10.3389/fcvm.2026.1937933

Image Credits: AI Generated

DOI: 10.3389/fcvm.2026.1937933

Keywords: Fontan circulation, cardiovascular magnetic resonance, superior vena cava flow, heart transplantation, congenital heart disease, risk stratification, ventricular function, moderate altitude, flow quantification, retrospective cohort, Cardiovascular, magnetic

In a groundbreaking advancement poised to revolutionize photodynamic therapy, researchers at Tsinghua University, China, have unveiled a novel approach to rapidly produce singlet oxygen with unprecedented efficiency and precision. This achievement stems from integrating the principles of bound states in the continuum (BIC) into meticulously engineered metasurfaces, marking a significant leap beyond the limitations that have hampered traditional molecular photosensitizers for decades.

Singlet oxygen, the excited state of molecular oxygen with formidable cytotoxic capabilities, has long been a cornerstone in targeting tumor cells via photodynamic therapy. Conventional production methods rely heavily on molecular photosensitizers, which suffer from inherent drawbacks such as photobleaching, limited wavelength selectivity, and biocompatibility issues. Metallic and semiconductor nanostructures emerged as alternatives due to their photostability; however, their quantum yields for singlet-oxygen generation remained too low to enable rapid, localized therapeutic outcomes under clinically viable low-dose illumination.

The breakthrough by Prof. Xing Fu and Prof. Qiang Liu’s team transcends these constraints by leveraging quasi-bound states in the continuum within an innovative Au–TiO₂ metasurface design. This architecture comprises elliptical TiO₂ nanopillars capped with an ultrathin 7 nm gold layer, engineered with subtle symmetry breaking that transforms a theoretically non-radiative BIC into a radiative quasi-BIC resonance. This purposeful symmetry perturbation dramatically enhances visible-light absorption at 532 nm, achieving an impressive 45% absorption within an optical path mere hundreds of nanometers thick. Such efficiency in light capture is vital to triggering the subsequent photochemical processes.

Under continuous-wave laser excitation, the metasurface’s enhanced near-field intensities lead to a marked elevation of the electronic temperature in the gold layer. This phenomenon facilitates the generation of energetic “hot carriers,” electrons that possess sufficient energy to inject into the conduction band of TiO₂. These injected electrons then catalyze interfacial redox reactions with the surrounding oxygen molecules, converting the triplet ground state into the highly reactive singlet oxygen species. The geometric design ensures that this reaction zone is tightly confined adjacent to the metasurface, enabling a concentrated and narrowly localized reactive oxygen environment.

Critically, the researchers have circumvented a prevailing issue in photocatalysis: the trade-off between metal loading and carrier lifetime. Typically, increasing metallic content amplifies light absorption but simultaneously accelerates carrier recombination, thus hindering catalytic efficiency. By maintaining an ultra-thin gold layer and leveraging the quasi-BIC resonance, the team achieved robust absorption with minimal metal volume, preserving extended carrier lifetimes and promoting efficient charge transfer.

One of the most remarkable outcomes of this advancement is the striking enhancement in singlet-oxygen quantum yield—surpassing conventional methods by an astonishing six orders of magnitude. This rapid, molar-level production occurs within mere seconds of illumination at continuous-wave operation, signifying a quantum leap in both speed and scale of reactive oxygen species generation suitable for therapeutic and chemical applications.

Beyond sheer efficiency, the metasurface’s resonant properties offer programmable selectivity. By geometrically scaling the nanopillar array, the resonance wavelength can be precisely tuned, enabling selective activation at desired illumination wavelengths. This spectral addressability facilitates spatially resolved cytotoxic effects, with demonstrated pixel-wise control over tumor-cell apoptosis guided by patterned illumination. Notably, this approach obviates the need for molecular photosensitizers, thereby sidestepping associated stability and compatibility issues.

The interplay of plasmonic and dielectric components within the metasurface underpins these photochemical innovations. While gold nanoparticles have historically served as hot-carrier generators in photocatalytic systems, coupling with TiO₂ elliptical nanopillars tuned near their BIC transitions magnifies the near-field enhancement and modulates charge dynamics. This synergy represents a paradigm shift in designing photocatalytic interfaces tailored for high-efficiency photon-to-chemical conversions.

Moreover, the localized generation of singlet oxygen holds significant promise for clinical applications beyond photodynamic cancer therapy. The capacity for rapid, spatially precise reactive species generation could impact selective oxidation reactions in chemical synthesis, environmental remediation, and microfluidic reactor technologies. The ability to deploy low doses of light while achieving targeted chemical effects is a profound advantage in reducing collateral damage and enhancing process efficiency.

The concept of engineering quasi-BIC states in metasurfaces to facilitate photocatalysis exemplifies the convergence of photonics and catalysis, leveraging wave-matter interactions for chemical control at the nanoscale. By translating this fundamental physics insight into a practical device architecture, the Tsinghua team has established a versatile platform that could be extended to diverse catalytic and sensing applications demanding high spatiotemporal precision.

In sum, the research showcases a compelling instance where advanced materials design, nanophotonics, and surface chemistry intersect to address longstanding challenges in reactive oxygen species generation. The quasi-BIC metasurface paradigm not only provides a robust solution for the rapid generation of singlet oxygen at therapeutic scales but also introduces a new dimension of control and efficiency that could redefine the capabilities of photodynamic therapy and beyond.

The publication in Light: Science & Applications stands as a testament to these interdisciplinary achievements. As the authors highlight, “BIC-engineered metasurfaces offer a generalizable route for efficient photon-to-chemical conversion at solid–liquid interfaces, unlocking immediate opportunities in photodynamic therapy, selective oxidation, and microreactor technologies where both low light dose and geometric precision are paramount.”

This pioneering work opens the door to further exploration of BIC and quasi-BIC states in nanophotonic structures tailored for catalytic applications, signaling a shift towards engineered nanoscale systems that harness light with exquisite control for biomedical and chemical innovations.

Subject of Research: Nanoscale photonics, photocatalysis, and photodynamic therapy.

Article Title: Quasi-BIC metasurfaces enable rapid, localized singlet-oxygen generation

News Publication Date: 2026 (exact date not specified)

Web References: DOI 10.1038/s41377-026-02267-9

Image Credits: Xing Fu et al.

For more than four and a half millennia, the Khufu Pyramid has stood on the Giza plateau, enduring dozens of earthquakes without serious structural damage.

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