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).

Background Left atrial size is an established marker of risk for adverse outcomes in heart failure with preserved ejection fraction (HFpEF). However, the independent prognostic importance of LA function in HFpEF is not known. Methods and Results We assessed LA function measured by speckle tracking echocardiography in 357 HFpEF patients enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial who were in sinus rhythm at the time of echocardiography. Lower peak LA strain, indicating LA dysfunction, was associated with older age, higher prevalence of atrial fibrillation and LV hypertrophy, worse LV and RV systolic function, and worse LV diastolic function. At a mean follow-up of 31 months (IQR 18 – 43months), 91 patients (25.5%) experienced the primary composite endpoint of CV death, HF hospitalization, and aborted sudden death. Lower peak LA strain was associated with a higher risk of the composite endpoint (HR 0.96 per unit of reduction in strain, 95% CI 0.94-0.99; p=0.009) and of HF hospitalization alone (HR 0.95 per unit of reduction in strain, 95% CI 0.92-0.98; p=0.003). The association of LA strain with incident HF hospitalization remained significant after adjustment for clinical confounders, but not after further adjustment for LV global longitudinal strain and the E/E′ ratio, parameters of LV systolic and diastolic function respectively. Conclusions LA dysfunction in HFpEF is associated with a higher risk of HF hospitalization independent of potential clinical confounders, but not independent of LV strain and filling pressure. Impairment in LV systolic and diastolic function largely explain the association between impaired LA function and higher risk of HF hospitalization in HFpEF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

AimsWomen are more likely to develop heart failure with preserved ejection fraction (HFpEF) than men. We studied the relationship between sex and cardiovascular structure and function in patients with HFpEF. Methods and resultsThe study included 279 participants from the PARAMOUNT study (57% women) with analysable baseline echocardiograms (mean age 71 years, 94% hypertensive, 38% diabetic). We assessed sex-based differences in baseline clinical characteristics and measures of cardiovascular structure/function. Coronary artery disease was less common in women than in men. Women were more obese and symptomatic, and less likely to have albuminuria. Women had higher indexed left ventricular (LV) wall thicknesses, worse diastolic function (lower E ′ , P = 0.002; higher E/E ′ , P < 0.001), while LV mass and LV volumes indexed for height 2.7 were similar. Nonetheless, female sex was associated with a trend towards higher prevalence of abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) at baseline (unadjusted P = 0.028, adjusted P = 0.056) and 12 weeks' follow up (unadjusted P = 0.001, adjusted P = 0.006), but not at 36 weeks' follow up (unadjusted P = 0.81, adjusted P = 0.99). Despite higher LV ejection fraction in women, global LV strain was similar between the sexes, while Tissue Doppler Imaging S ′ mitral velocity was lower in women. Both LV diastolic and systolic stiffness were higher in women than men (P < 0.001), even adjusting for LV concentricity and clinical covariates. We observed no sex differences in systolic arterial-LV coupling, as women also had higher absolute arterial elastance compared with men, although this difference was not significant after adjusting for height 2.7 .

Aims Left atrial (LA) enlargement is present in the majority of heart failure with preserved ejection fraction (HFpEF) patients and is a marker of risk. However, the importance of LA function in HFpEF is less well understood. Methods and Results The PARAMOUNT trial enrolled HFpEF patients (LVEF ≥ 45%, NT-proBNP > 400 pg/ml). We assessed LA reservoir, conduit and pump function using 2D volume indices and speckle tracking echocardiography in 135 HFpEF patients in sinus rhythm at the time of echocardiography and 40 healthy controls of similar age and gender. LA strain was related to clinical characteristics and measures of cardiac structure and function. Compared to controls, HFpEF patients had worse LA reservoir, conduit, and pump function. The differences in systolic LA strain (Controls, 39.2 ± 6.6% vs HFpEF, 24.6 ± 7.3%) between groups remained significant after adjustments and even in the subsets of HFpEF patients with normal LA size or without a history of AF. Among HFpEF patients, lower LA strain was associated with higher prevalence of prior HF hospitalization and history of AF, as well as worse LV systolic function, higher LV mass and LA volume. However, NT-proBNP and E/E’ were similar across the quartiles of LA function. Conclusions In this HFpEF cohort, we observed impairment in all phases of LA function, and LA strain was decreased independent of LA size or history of AF. LA dysfunction may be a marker of severity and play a pathophysiologic role in HFpEF. Clinical Trial Registration (Clinicaltrials.gov NCT00887588)