Early-stage heart failure with preserved ejection fraction in the pig: a cardiovascular magnetic resonance study.
BACKGROUND
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.


METHODS
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 (VV(int/LV)) and collagen (VV(coll/LV)). Rest, stress, and stress-to-rest differences of cardiac and myocardial parameters in DOCA and control animals were compared by t-test.


RESULTS
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 VV(int/LV) did not differ between groups, whereas VV(coll/LV) levels were higher in DOCA pigs (p = 0.044).


CONCLUSIONS
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.


BACKGROUND
The study was approved by the local Bioethics Committee of Vienna, Austria (BMWF-66.010/0091-II/3b/2013).
Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9/P, 8036, Graz, Austria. ursula.reiter@medunigraz.at.
Ursula
U
Reiter
Siemens Healthcare, Graz, Austria.
Gert
G
Reiter
Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Martin
M
Manninger
Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9/P, 8036, Graz, Austria.
Gabriel
G
Adelsmayr
Hannover Medical School, Institute of Functional and Applied Anatomy, Hannover, Germany.
Julia
J
Schipke
Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.|Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, Berlin, Germany.
Alessio
A
Alogna
Hannover Medical School, Institute of Functional and Applied Anatomy, Hannover, Germany.
Alexandra
A
Rajces
Siemens Healthcare GmBH, Erlangen, Germany.
Aurelien F
AF
Stalder
Siemens Healthcare GmBH, Erlangen, Germany.
Andreas
A
Greiser
Hannover Medical School, Institute of Functional and Applied Anatomy, Hannover, Germany.
Christian
C
Mühlfeld
Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Daniel
D
Scherr
Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, Berlin, Germany.
Heiner
H
Post
Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.|Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, Berlin, Germany.|Department of Internal Medicine and Cardiology, German Heart Center Berlin, Berlin, Germany.|Berlin Institute of Health, Berlin, Germany.
Burkert
B
Pieske
Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9/P, 8036, Graz, Austria.
Michael
M
Fuchsjäger
Cardiovascular magnetic resonance; Diastolic dysfunction; Dobutamine stress; Heart failure with preserved ejection fraction; Porcine model
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