Diastolic Dysfunction in Congenital Heart Disease: A Pressure-Volume Loop Analysis of Borderline Left Heart

Background Diastolic dysfunction is a major driver of morbidity in congenital heart disease (CHD), but its mechanisms are poorly understood. It remains unknown whether left ventricular (LV) diastolic dysfunction in borderline left heart patients is caused by a defect in active relaxation or in passive compliance. Objectives We sought to apply gold-standard pressure-volume (PV) loop analysis to define the primary mechanism of diastolic dysfunction in patients with borderline LV (bLV). Methods We analyzed invasive PV loop data from pediatric patients with bLV (n =13) and a comparison group of patients with congenitally corrected transposition of the great arteries (ccTGA, presumed no diastolic dysfunction; n=14). PV loops were generated during transient preload reduction and augmentation. Active relaxation was assessed by the isovolumic relaxation time-constant (τ) and maximal rate of pressure decline (dP/dt min ) indexed to peak-systolic pressure (PSP). Passive compliance was quantified by the chamber stiffness constant (β), derived from the multi-beat end-diastolic PV relationship (EDPVR). To account for size differences, β was (1) calculated using indexed ventricular volumes (iβ), and (2) converted to a dimensionless stiffness constant (β W ) by multiplying β by ventricular wall volume. Results Active relaxation measures were similar between groups, indicating normal lusitropy in bLV (τ bLV: 28 [23.5-29.5] vs ccTGA: 24 [21-28] msec, p=0.10; dP/dt min /PSP bLV: -10.6 [-11.0, -9.4] vs. ccTGA: -9.9 [-10.5, -8.7] s -1 , p=0.17). In contrast, patients with bLV had markedly abnormal passive compliance. The EDPVR was shifted sharply upward and to the left, and the stiffness constants were significantly higher in the bLV group (iβ bLV: 0.10 [0.04-0.35] vs. ccTGA: 0.03 [0.02-0.04] m 2 /mL, p=0.003); β W bLV: 4.08 [1.60-7.52] vs. ccTGA: 1.21 [0.95-1.77], p=0.002). Conclusions The primary mechanism of diastolic dysfunction in bLV is impaired passive ventricular compliance, and not impaired active relaxation. These findings suggest a limited role for lusitropic medications and therapeutic strategies that focus on mitigating ventricular stiffness (such as surgical endocardial fibroelastosis resection) may be more valuable. Condensed abstract Pressure-volume loop analysis with preload alteration in pediatric congenital heart disease shows that in borderline left heart patients left ventricular diastolic dysfunction is caused by impaired passive compliance, with preserved active relaxation. This mechanistic insight suggests that interventions targeting ventricular stiffness such as surgical endocardial fibroelastosis resection may be more beneficial than the use of lusitropic medications to improve outcomes.