Changes in Myocardial Microstructure and Mechanics With Progressive Left Ventricular Pressure Overload.

This study assessed the regional changes in myocardial geometry, microstructure, mechanical behavior, and properties that occur in response to progressive left ventricular pressure overload (LVPO) in a large animal model. Using an index of local biomechanical function at early onset of LVPO allowed for prediction of the magnitude of left ventricular chamber stiffness (Kc) and left atrial area at LVPO late timepoints. Our study found that LV myocardial collagen content alone was insufficient to identify mechanisms for LV myocardial stiffness with progression to heart failure with preserved ejection fraction (HFpEF). Serial assessment of regional biomechanical function might hold value in monitoring the natural history and progression of HFpEF, which would allow evaluation of novel therapeutic approaches.

Torres WM ，Barlow SC ，Moore A ，Freeburg LA ，Hoenes A ，Doviak H ，Zile MR ，Shazly T ，Spinale FG ... -  《JACC-Basic to Translational Science》

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction.

Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF. 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin <100 μg/l or ferritin of 100-299 μg/l in combination with transferrin saturation <20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies. Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p<0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency. In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.

Kasner M ，Aleksandrov AS ，Westermann D ，Lassner D ，Gross M ，von Haehling S ，Anker SD ，Schultheiss HP ，Tschöpe C ... -  《-》

Impaired systolic function by strain imaging in heart failure with preserved ejection fraction.

This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF). Although diastolic dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined. We assessed myocardial systolic and diastolic function in 219 HFpEF patients from a contemporary HFpEF clinical trial. Myocardial deformation was assessed using a vendor-independent 2-dimensional speckle-tracking software. The frequency and severity of impaired deformation was assessed in HFpEF, and compared to 50 normal controls free of cardiovascular disease and to 44 age- and sex-matched hypertensive patients with diastolic dysfunction (hypertensive heart disease) but no HF. Among HFpEF patients, clinical, echocardiographic, and biomarker correlates of left ventricular strain were determined. The HFpEF patients had preserved left ventricular ejection fraction and evidence of diastolic dysfunction. Compared to both normal controls and hypertensive heart disease patients, the HFpEF patients demonstrated significantly lower longitudinal strain (LS) (-20.0 ± 2.1 and -17.07 ± 2.04 vs. -14.6 ± 3.3, respectively, p < 0.0001 for both) and circumferential strain (CS) (-27.1 ± 3.1 and -30.1 ± 3.5 vs. -22.9 ± 5.9, respectively; p < 0.0001 for both). In HFpEF, both LS and CS were related to LVEF (LS, R = -0.46; p < 0.0001; CS, R = -0.51; p < 0.0001) but not to standard echocardiographic measures of diastolic function (E' or E/E'). Lower LS was modestly associated with higher NT-proBNP, even after adjustment for 10 baseline covariates including LVEF, measures of diastolic function, and LV filling pressure (multivariable adjusted p = 0.001). Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588).

Kraigher-Krainer E ，Shah AM ，Gupta DK ，Santos A ，Claggett B ，Pieske B ，Zile MR ，Voors AA ，Lefkowitz MP ，Packer M ，McMurray JJ ，Solomon SD ，PARAMOUNT Investigators ... -  《-》

Heart failure with preserved ejection fraction in pigs causes shifts in post-transcriptional checkpoints.

Samani SL ，Barlow SC ，Freeburg LA ，Catherwood GM ，Churillo AM ，Jones TL ，Altomare D ，Ji H ，Shtutman M ，Zile MR ，Shazly T ，Spinale FG ... -  《-》

Ubiquitin ligase Wwp1 gene deletion attenuates diastolic dysfunction in pressure-overload hypertrophy.

Snyder LB ，Lai Y ，Doviak H ，Freeburg LA ，Laney VK ，Moore A ，Zellars KN ，Matesic LE ，Spinale FG ... -  《-》