Key result
DOCA-salt treatment in pigs induced early-stage heart failure with preserved ejection fraction, characterized by elevated left ventricular muscle mass and left atrial enlargement.
Why the study?
Does DOCA-salt treatment induce CMR-detectable changes characteristic of early-stage HFpEF in a pig model?
Does DOCA-salt treatment induce CMR-detectable changes characteristic of early-stage HFpEF in a pig model?
Answers are grounded in this paper and cite their sources.
CMR imaging in a DOCA-salt pig model of early-stage HFpEF reveals LA enlargement, reduced E', elevated E/E', and inadequate myocardial perfusion reserve during stress.
The hypertensive deoxy-corticosterone acetate (DOCA)-salt-treated pig (hereafter, DOCA pig) was recently introduced as large animal model for early-stage heart failure with preserved ejection fraction (HFpEF). The aim of the present study was to evaluate cardiovascular magnetic resonance (CMR) of DOCA pigs and weight-matched control pigs to characterize ventricular, atrial and myocardial structure and function of this phenotype model. Five anesthetized DOCA and seven control pigs underwent 3 T CMR at rest and during dobutamine stress. Left ventricular/atrial (LV/LA) function and myocardial mass (LVMM), strains and torsion were evaluated from (tagged) cine imaging. 4D phase-contrast measurements were used to assess blood flow and peak velocities, including transmitral early-diastolic (E) and myocardial tissue (E’) velocities and coronary sinus blood flow. Myocardial perfusion reserve was estimated from stress-to-rest time-averaged coronary sinus flow. Global native myocardial T1 times were derived from prototype modified Look-Locker inversion-recovery (MOLLI) short-axis T1 maps. After in-vivo measurements, transmural biopsies were collected for stereological evaluation including the volume fractions of interstitium (V V (int/LV)) and collagen (V V (coll/LV)). Rest, stress, and stress-to-rest differences of cardiac and myocardial parameters in DOCA and control animals were compared by t -test. In DOCA pigs LVMM ( p < 0.001) and LV wall-thickness (end-systole/end-diastole, p = 0.003/ p = 0.007) were elevated. During stress, increase of LV ejection-fraction and decrease of end-systolic volume accounted for normal contractility reserves in DOCA and control pigs. Rest-to-stress differences of cardiac index ( p = 0.040) and end-diastolic volume ( p = 0.042) were documented. Maximal ( p = 0.042) and minimal ( p = 0.012) LA volumes in DOCA pigs were elevated at rest; total LA ejection-fraction decreased during stress ( p = 0.006). E’ was lower in DOCA pigs, corresponding to higher E/E’ at rest ( p = 0.013) and stress ( p = 0.026). Myocardial perfusion reserve was reduced in DOCA pigs ( p = 0.031). T1-times and V V (int/LV) did not differ between groups, whereas V V (coll/LV) levels were higher in DOCA pigs ( p = 0.044). LA enlargement, E’ and E/E’ were the markers that showed the most pronounced differences between DOCA and control pigs at rest. Inadequate increase of myocardial perfusion reserve during stress might represent a metrics for early-stage HFpEF. Myocardial T1 mapping could not detect elevated levels of myocardial collagen in this model. The study was approved by the local Bioethics Committee of Vienna, Austria (BMWF-66.010/0091-II/3b/2013).
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Reiter et al. (2016) studied Early-stage heart failure with preserved ejection fraction (HFpEF) (n=12). DOCA-salt treatment vs. Weight-matched healthy controls was evaluated on Left ventricular muscle mass (LVMM) at rest (p=<0.001). DOCA-salt treatment in pigs induced early-stage heart failure with preserved ejection fraction, characterized by elevated left ventricular muscle mass and left atrial enlargement.
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