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

While the recreational use of marijuana is usually associated with a more peaceful mental state, scientists just a made a surprising discovery.

As detailed in a meta analysis of cannabis-related studies published last month in the journal Psychological Medicine, a team of scientists in the UK discovered a significant link between cannabis use and an “increased risk of violence.”

The headline finding was that they found cannabis users were statistically more likely to be the perpetrators of violent acts. They also found that the use of the drug — particularly among women and mixed-gender cohorts — was “significantly associated with an increased risk of becoming a victim of violence” as well.

While it’s a classic case of correlation, not causation — the researchers stop far short of suggesting the drug directly motivates users to be more violent as we’re far from reaching a scientific consensus on the matter — the findings “underscore the importance of addressing this issue at both a societal and clinical level,” according to the paper.

In other words, it’s a highly nuanced and complex relationship with plenty of other factors at play.

“As a clinician, I’ve seen how heavy cannabis use can be a factor in violence,” said coauthor and King’s College London professor Marta Di Forti in a statement. “We’ve been cautious for a long time about how far we could go in describing this link, but a review of this size lets us speak with more confidence about the risks, while being careful not to stigmatise people who use cannabis more broadly.”

“As cannabis becomes more commercialized and legalised around the world, the conversation about its risks has focused mostly on the person using it,” added coauthor and King’s College London professor of psychiatric research Sir Robin Murray. “This review shows that violence, both committing it and experiencing it, needs to be part of that conversation too.”

For their paper, the researchers examined 63 cannabis-related studies, involving just over 265,000 subjects.

The researchers found that cannabis users “may place themselves in risky situations,” which could help explain the “increased vulnerability” to violence. Users may also be exposed to “peers who engage in substance use or criminal activities.”

The risk of violence was also more pronounced among psychiatric patients. Previous resarch has found that people who already suffer from pre-existing mental conditions such as psychosis may experience “poorer clinical outcomes” through continued cannabis use.

“Given the higher rate of cannabis use among individuals with severe mental disorders compared to the general population, this group represents a particularly at-risk population in terms of violent behavior,” the paper reads.

The researchers offered some key takeaways from their findings. At the societal level, the researchers suggest that “violence should be considered alongside other established cannabis-related harms when developing prevention strategies, public education campaigns, and regulatory policies.”

At the clinical level, the research highlights the “necessity for mental health professionals to routinely assess cannabis use in individuals presenting with violent tendencies, particularly among those with severe mental illness.”

However, to get a better picture of how cannabis use relates to violence, future studies will need to “disentangle causal pathways” by diving into how, why, and when people use the drug in more detail. Other studies should also “examine whether reducing cannabis use through clinical or public health interventions leads to reductions in violent behavior,” the researchers conclude.

More on marijuana: Research Suggests the Older You Get, the More Weed You Should Smoke

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