Increased stiffness is the major early abnormality in a pig model of severe aortic stenosis and predisposes to congestive heart failure in the absence of systolic dysfunction

Background: it remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis.methods and results: yorkshire pigs underwent surgical banding of the ascending aorta. the animals were followed for up to 5 months after surgery,and cardiac function was assessed comprehensively by invasive pressure-volume measurements,3-dimensional echocardiography,echocardiographic speckle-tracking strain,and postmortem molecular and histological analyses. pigs with aortic banding (n=6) exhibited significant left ventricular hypertrophy with increased stiffness compared with the control pigs (n=7) (end-diastolic pressure-volume relationship β: 0.053±0.017 versus 0.028±0.009 mm hg/ml,p=0.007); however,all other parameters corresponding to systolic function,including ejection fraction,end-systolic pressure-volume relationship,preload recruitable stroke work,echocardiographic circumferential strain,and longitudinal strain,were not impaired in pigs with aortic banding. relaxation parameters were also similar between groups. sarcoplasmic reticulum calcium (ca(2+)) atpase protein levels in the left ventricle were similar. there were significant increases in 3-dimensional echocardiographic left atrial volumes,suggesting the usefulness of these indexes to detect increased stiffness. right atrial pacing with a heart rate of 120 beats per minute induced increased end-diastolic pressure in pigs with aortic banding in contrast to decreased end-diastolic pressure in the control pigs. histological evaluation revealed that increased stiffness was accompanied by cardiomyocyte hypertrophy and increased perimysial and perivascular fibrosis.conclusion: increased stiffness is the major early pathological process that predisposes to congestive heart failure without abnormalities in systolic function and relaxation in a clinically relevant animal model of aortic stenosis. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.