Diastolic Dysfunction in Congenital Heart Disease: A Pressure-Volume Loop Analysis of Borderline Left Heart
Nikhil Thatte, Martin Liberman, Peter E. Hammer, Ryan Callahan, Jesse Esch, Michael Farias, Gerald Marx, Rebecca S. Beroukhim, Eric Feins, Sitaram Emani, Sunil J. GhelaniBACKGROUND:
Diastolic dysfunction is a major driver of morbidity in congenital heart disease, 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 stiffness. We applied gold-standard pressure-volume (PV) loop analysis to define the mechanism of diastolic dysfunction in patients with borderline LV.
METHODS:
We analyzed invasive PV loops from children with bLV (n=13) and a pragmatic comparison group of patients with congenitally corrected transposition of the great arteries (ccTGA, n=14). PV loops were generated during transient preload alteration. Active relaxation was assessed by the isovolumetric relaxation time constant (τ) and maximal rate of pressure decline (dP/dt min ) indexed to peak systolic pressure. Passive stiffness was quantified by the stiffness constant (β), derived from the multibeat end-diastolic PV relationship. To account for size differences, β was calculated using indexed ventricular volumes (iβ), and also converted to a dimensionless stiffness constant (β w =β×ventricular wall volume).
RESULTS:
Active relaxation measures were similar between groups (τ bLV, 28 [23.5–29.5] versus ccTGA, 24 [21–28] msec,
CONCLUSIONS:
The primary mechanism of diastolic dysfunction in bLV is increased passive ventricular stiffness, while no differences were detected in 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.