Assessment of Atrioventricular and Ventriculoarterial Coupling Indices in Patients with Hypoplastic Left Heart Syndrome Utilizing Cardiac MRI and Invasive Hemodynamics

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Hypoplastic left heart syndrome (HLHS) with stage II palliation undergoing pre-Fontan evaluation (n=45). Intervention: Novel RA-RV-Aorta coupling index and RAsv-RV coupling index vs. Known atrioventricular and ventriculoarterial (RV-Aortic) coupling indices. Primary outcome: Composite adverse clinical outcome (death, heart transplantation, heart failure hospitalization, SGLT2 inhibitor initiation, plastic bronchitis, or protein-losing enteropathy) (OR 0.36, 95% CI 0.12-0.73, p=0.001).

Q: What does this research mean for the field?

Novel single-ventricle coupling indices, particularly the combined RA-RV-Aorta coupling index, strongly predict adverse outcomes in stage II hypoplastic left heart syndrome patients and outperform traditional atrioventricular coupling measures. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Aidan J Reid; Morgan L. MacBeth; Jennifer Romanowicz; Benjamin S. Frank; Cesar Gonzalez Alba

doi:10.21203/rs.3.rs-11089318/v1

October 14, 2026Open Access

Assessment of Atrioventricular and Ventriculoarterial Coupling Indices in Patients with Hypoplastic Left Heart Syndrome Utilizing Cardiac MRI and Invasive Hemodynamics

View Full Paper

Ask AI

Bookmark

Share

Key result

Novel RA-RV-Aorta coupling index linked to ~64% lower odds of adverse stage II HLHS outcomes.

OR 0.36
95% CI 0.12-0.73
P=0.001
n=45

Why the study?

Atrioventricular and ventriculoarterial coupling indices have demonstrated prognostic value in various cardiac pathologies, but their utility for predicting adverse outcomes in hypoplastic left heart syndrome had not been studied.

Do novel atrioventricular and ventriculoarterial coupling indices derived from cardiac MRI and invasive hemodynamics improve prediction of adverse clinical outcomes compared to known coupling indices in patients with hypoplastic left heart syndrome and stage II palliation prior to Fontan completion?

Key Points

To evaluate whether known and novel atrioventricular and ventriculoarterial coupling indices derived from cardiac MRI and invasive hemodynamics predict adverse clinical outcomes in patients with hypoplastic left heart syndrome before Fontan completion.
Retrospectively analyzed cardiac MRI and invasive catheterization data from 45 patients with hypoplastic left heart syndrome following stage II palliation evaluated between January 2015 and October 2025.
Evaluated known atrioventricular coupling indices alongside two novel indices: the right atrial stroke volume to right ventricular coupling index and the combined right atrial-right ventricular-aortic coupling index.
Assessed predictive discrimination for a composite adverse outcome (death, heart transplantation, heart failure hospitalization, SGLT2 inhibitor initiation, plastic bronchitis, or protein-losing enteropathy) using Firth logistic regression and ROC analysis.
Ten of 45 patients (22%) experienced the composite adverse outcome, including 4 heart transplantations, 3 heart failure events, 1 plastic bronchitis, 1 protein-losing enteropathy, and 1 death.
Known atrioventricular coupling indices did not significantly differ between groups (AUC 0.48–0.69), whereas RV-aortic coupling was significantly lower in patients with adverse outcomes (0.17 vs. 0.23, p = 0.006; AUC = 0.80).
Both novel indices demonstrated superior predictive discrimination: novel right atrial stroke volume to RV coupling (0.11 vs. 0.17, p = 0.002; AUC = 0.82) and novel right atrial-RV-aorta coupling (2.13 vs. 3.90, p = 0.001; AUC = 0.86), significantly improving model fit over RV-aortic coupling alone (p = 0.036 and p = 0.048, respectively).

Study Design

Type

Cohort (n=45)

Multicenter

No

Structured PICO

Do novel atrioventricular and ventriculoarterial coupling indices derived from cardiac MRI and invasive hemodynamics improve prediction of adverse clinical outcomes compared to known coupling indices in patients with hypoplastic left heart syndrome and stage II palliation prior to Fontan completion?

P

Population

45 pediatric patients (36% female, median age ~2.8 years) with hypoplastic left heart syndrome and stage II palliation undergoing pre-Fontan cardiac MRI and catheterization evaluation, followed up to a median age of 80 months.

E

Exposure

Assessment using two novel coupling indices designed for single ventricle physiology derived from CMR and invasive hemodynamics: novel RAsv-RV coupling index (right atrial stroke volume indexed / right ventricular end-diastolic volume indexed) and combined novel RA-RV-Aorta coupling index ((RVGLS/RVSP)(RASVi/RVEDVi)*100).

C

Comparator

Known atrioventricular (AV) coupling indices (RACI, RAVCVOL, RASTIFF, RAVCFT) and known ventriculoarterial (VA) RV-Aortic coupling index ([RVGLS/RVSP]-1).

O

Outcome

Composite of adverse clinical outcomes including death, heart transplantation, heart failure symptomatology requiring hospital admission or initiation of a SGLT2 inhibitor, and a diagnosis of plastic bronchitis or protein-losing enteropathy.composite

Main Result

Odds Ratio: 0.36 (95% CI 0.12–0.73)

Absolute Event Rate: 2.13% vs 3.9%

p-value: p=0.001

Novel atrioventricular and ventriculoarterial coupling indices tailored for single ventricle physiology (RAsv-RV and RA-RV-Aorta) outperform standard biventricular AV coupling metrics and provide incremental prognostic value beyond RV-Aortic coupling alone for predicting adverse clinical outcomes in HLHS patients undergoing pre-Fontan evaluation.

Limitations

Single-center retrospective study with a relatively small sample size (N=45) and limited outcome events (n=10)
Use of specific commercial software for CMR feature-tracking strain analysis may introduce bias and limit generalizability
Right atrial volumes were calculated from a single 4-chamber CMR slice in patients with distorted atrial anatomy following atrial septectomy
Patients who did not proceed to Fontan completion based on pre-operative assessments were not included in post-Fontan analyses
Single-center retrospective study design
Relatively small sample size (n=45) with a small number of outcome events (n=10)
Specific commercial software was utilized for CMR strain analysis which may introduce bias and reduce generalizability
RA volumes were calculated from a single 4-chamber CMR slice in a population with distorted atrial anatomy after atrial septectomy

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

May improve pre-Fontan risk stratification in HLHS; extends coupling indices to single-ventricle physiology but remains hypothesis-generating.

Abstract

Background Atrioventricular (AV) and ventriculoarterial (VA) coupling indices have demonstrated prognostic value in various cardiac pathologies but have not been studied in hypoplastic left heart syndrome (HLHS). This study assessed known and novel AV and VA coupling indices derived from cardiac MRI (CMR) and invasive hemodynamics for predicting adverse outcomes in HLHS patients with stage II palliation prior to Fontan completion. Methods CMR and catheterization data from 45 HLHS patients with stage II palliation undergoing pre-Fontan evaluation (January 2015–October 2025) were retrospectively analyzed. Known AV coupling indices and two novel indices—RA SV -RV coupling index (RA stroke volume indexed/RV end-diastolic volume indexed) and combined RA-RV-Aorta coupling index—were compared between patients with and without adverse outcomes (composite of death, transplantation, heart failure hospitalization, SGLT2 inhibitor initiation, plastic bronchitis, protein-losing enteropathy). Predictive performance was assessed using Firth logistic regression and ROC analysis. Results Ten patients (22%) experienced adverse outcomes. Known AV coupling indices did not significantly differ between groups (AUC 0.48–0.69). The RV-Aortic coupling index was significantly lower in the adverse outcomes group (0.17 vs. 0.23, p = 0.006; AUC = 0.80). Both novel indices demonstrated superior discrimination: RA SV -RV (0.11 vs. 0.17, p = 0.002; AUC = 0.82) and novel RAsv-RV-Aorta (2.13 vs. 3.90, p = 0.001; AUC = 0.86). Nested models showed that adding each novel index to RV-Aortic coupling significantly improved model fit (p = 0.036 and p = 0.048, respectively). Conclusions Novel coupling indices designed for single ventricle physiology outperformed known AV coupling indices and provided incremental predictive value beyond RV-Aortic coupling alone for adverse outcomes in HLHS patients with stage II palliation.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Reid et al. (2026) conducted a cohort in Hypoplastic left heart syndrome (HLHS) with stage II palliation undergoing pre-Fontan evaluation (n=45). Novel RA-RV-Aorta coupling index and RAsv-RV coupling index vs. Known atrioventricular and ventriculoarterial (RV-Aortic) coupling indices was evaluated on Composite adverse clinical outcome (death, heart transplantation, heart failure hospitalization, SGLT2 inhibitor initiation, plastic bronchitis, or protein-losing enteropathy) (OR 0.36, 95% CI 0.12-0.73, p=0.001). Novel RA-RV-Aorta coupling index strongly predicted adverse outcomes in stage II HLHS patients, outperforming known atrioventricular coupling indices.

synapsesocial.com/papers/6ae682a3e432e7a5c4ef35ef https://doi.org/10.21203/rs.3.rs-11089318/v1

View Full Paper

Ask AI

Bookmark

Share

Assessment of Atrioventricular and Ventriculoarterial Coupling Indices in Patients with Hypoplastic Left Heart Syndrome Utilizing Cardiac MRI and Invasive Hemodynamics

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Assessment of Atrioventricular and Ventriculoarterial Coupling Indices in Patients with Hypoplastic Left Heart Syndrome Utilizing Cardiac MRI and Invasive Hemodynamics

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading