• cardiac remodeling
• cardiomyocyte
• diastolic dysfunction
• fibrosis
• heart failure
• heart failure with preserved ejection fraction
• natriuretic peptides

Aims: In HFpEF patients plasma levels of natriuretic peptides (NP) are frequently low and in several HFpEF trials outcomes differed between patients with low and high NP levels. Structural and functional differences of echocardiographic LV remodeling in chronic HFpEF patients with low and high NP levels were therefore investigated.
Methods and Results: Data of 83 stable HFpEF patients were derived from routine outpatient clinic visits. A gender-matched control group without cardiovascular disease (n=33) was identified.
Median NT-proBNP was 161 pg/ml with 34.9 % of HFpEF patients below the diagnostic cut-off value of 125 pg/ml and 68.7 % of HFpEF patients below the eligibility threshold used in trials (<300 pg/ml). When HFpEF patients with below median NT-proBNP were compared to controls, HFpEF patients had LV concentric remodeling, worse LV systolic function, slower LV relaxation and higher LV diastolic stiffness. When HFpEF patients with below median NT-proBNP were compared to HFpEF patients with above median NT-proBNP, LV concentric remodeling, LV systolic function and LV relaxation were comparable but LV diastolic stiffness continued to deteriorate. On multiple linear regression analysis especially measures of LV stiffness significantly related to NT-proBNP.
Conclusions: When echocardiographic LV remodeling and dysfunction were compared in HFpEF patients with below and above median NT-proBNP, concentric LV remodeling, systolic LV dysfunction and slow LV relaxation were similar in both groups but diastolic LV stiffness worse in patients with above median NT-proBNP. Failure to improve LV stiffness could have contributed to the neutral outcome of trials in patients with high NT-proBNP.