Background: A novel paradigm of diastolic heart failure with preserved ejection fraction (HFpEF) proposed the induction of coronary microvascular dysfunction by HFpEF comorbidities via a systemic pro-inflammatory state and associated oxidative stress. The consequent nitric oxide deficiency would increase diastolic tension and favor fibrosis of adjacent myocardium, which implies not only left ventricular (LV), but all-chamber myocardial stiffening. Our aim was to assess relations between low-grade chronic systemic inflammation and left atrial (LA) pressure-volume relations in real-world HFpEF patients.
Methods: We retrospectively analyzed medical records of 60 clinically stable HpEFF patients in sinus rhythm with assayed high-sensitive C-reactive protein (CRP) during the index hospitalization. Subjects with CRP >10 mg/L or coexistent diseases, including coronary artery disease, were excluded. LV and LA diameters and mitral E/E' ratio (an index of LA pressure) were extracted from routine echocardiographic records. A surrogate measure of LA stiffness was computed as the averaged mitral E/e' ratio divided by LA diameter.
Results: With ascending CRP tertiles, we observed trends for elevated mitral E/e' ratio (p <0.001), increased relative LV wall thickness (p = 0.01) and higher NYHA functional class (p = 0.02). The LA stiffness estimate and log-transformed CRP levels (log-CRP) were interrelated (r = 0.38, p = 0.003). On multi- variate analysis, the LA stiffness index was independently associated with log-CRP (β ± SEM: 0.21 ± 0.07, p = 0.007) and age (β ± SEM: 0.16 ± 0.07, p = 0.03), which was maintained upon adjustment for LV mass index and relative LV wall thickness.
Conclusions: Low-grade chronic inflammation may contribute to LA stiffening additively to age and regardless of the magnitude of associated LV hypertrophy and concentricity. LA stiffening can exacerbate symptoms of congestion in HFpEF jointly with LV remodeling.
Keywords: echocardiography; heart failure with preserved ejection fraction; le atrium; left ventricle; low-grade chronic inflammation.