Diastolic dysfunction precedes systolic failure in experimental right ventricular overload: a systematic review
C Kocx, J Healy, A Hemnes, S Lal, D S CelermajerAbstract
Background
Right ventricular (RV) diastolic dysfunction may represent an early, therapeutically targetable phase of RV failure, yet the temporal relationship between diastolic impairment and systolic decompensation across experimental models has not been systematically characterised.
Methods
Following PRISMA guidelines and prospective registration, we systematically searched MEDLINE, Embase, and Scopus for animal studies reporting RV diastolic parameters. Extraction with independent verification captured invasive indices (RVEDP, Tau, EDPVR), imaging parameters, and systolic function across pressure overload, volume overload, and experimental disease models. Evidence was synthesised narratively across temporal phases: acute (<7 days), subacute (1–4 weeks), intermediate (1–3 months), and chronic (>3 months).
Results
We included 127 studies (473 experimental groups) spanning six decades of RV physiology research. A consistent temporal sequence emerged across pressure overload models: diastolic impairment, manifest as elevated RVEDP and prolonged relaxation, was detectable within hours to days of loading, whereas systolic pressure elevation and contractile augmentation emerged over weeks. Notably, systolic indices (dP/dT max, Ees) typically increased rather than decreased, indicating compensatory hyperdynamic function rather than early systolic failure. Disease models (MCT, SuHx) demonstrated marked diastolic dysfunction at standard 3–4 week endpoints, while volume overload showed a distinct pattern with delayed diastolic impairment emerging at 1–3 months. Ventricular interdependence (septal shift impairing LV filling) was consistently reported in studies with biventricular assessment, though only 14% of studies provided such data.
Conclusions
This systematic review identifies diastolic dysfunction as an early detectable RV abnormality under pressure stress, preceding systolic changes by days to weeks. This pattern appears to be replicated in volume, mixed and experimental disease loading modelsm, however this is with a lesser degree of certainty. The temporal primacy of diastolic impairment supports early assessment of RV filling pressures in patients at risk for RV failure and suggests a potential therapeutic window before the transition to overt systolic decompensation.