Background Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (i.e., LA strain measures) in HFpEF has not been well studied. We hypothesized that in HFpEF, reduced (worse) LA strain is a key pathophysiologic abnormality and is a stronger correlate of adverse events than left ventricular (LV) or right ventricular (RV) longitudinal strain. Methods and Results We evaluated baseline LA function in 308 patients with HFpEF who were followed longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of LV longitudinal strain, RV free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of LV, RV, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years; 64% were female; 26% had atrial fibrillation; and LA enlargement was present in the majority (67%) of patients. Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the LV, RV, and LA strain measures, LA reservoir strain was the strongest correlate of adverse events, and was independently associated with the composite outcome of cardiovascular hospitalization or death (adjusted HR per 1-SD decrease in LA strain = 1.54; 95% CI = 1.15–2.07; P=0.006). Conclusions Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and/or augmentation of LA function may be important future therapeutic targets in HFpEF. Registration Information URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.

BACKGROUND. Left atrial (LA) and left ventricular (LV) remodeling are associated with atrial fibrillation (AF). The prospective associations of impairment in cardiac mechanical function, as assessed by speckle-tracking echocardiography, with incident AF are less clear. METHODS. In the Cardiovascular Health Study, a community-based cohort of older adults, participants free of AF with echocardiograms of adequate quality for speckle tracking were included. We evaluated the associations of indices of cardiac mechanics (LA reservoir strain, LV longitudinal strain, and LV early diastolic strain rate) with incident AF. RESULTS. Of 4341 participants with strain imaging, participants with lower LA reservoir strain were older, had more cardiometabolic risk factors, and had lower renal function at baseline. Over a median follow-up of 10 years, 497 (11.4%) participants developed AF. Compared with the highest quartile of LA reservoir strain, the lowest quartile of LA reservoir strain was associated with higher risk of AF after covariate adjustment, including LA volume and LV longitudinal strain (Hazard Ratio [HR], 1.80; 95% CI, 1.31-2.45; P < 0.001). The association of LA reservoir strain and AF was stronger in subgroups with higher blood pressure, NT-proBNP, and LA volumes. There were no associations of LV longitudinal strain and LV early diastolic strain rate with incident AF after adjustment for LA reservoir strain. CONCLUSION. Lower LA reservoir strain was associated with incident AF, independent of LV mechanics, and with stronger associations in high-risk subgroups. These findings suggest that LA mechanical dysfunction precedes the development of AF. Therapies targeting LA mechanical dysfunction may prevent progression to AF.

Pointsc Two-dimensional speckle-tracking echocardiography (2D-STE) can detect early changes in cardiac mechanics and may be able to identify individuals at risk for kidney disease progression. c Novel indices of cardiac mechanics on 2D-STE may identify a population that may benefit from early diagnosis, monitoring, and treatment. c Novel pharmacologic therapies may be beneficial in patients with subclinical myocardial dysfunction at risk for kidney function decline.

Introduction: A potential mechanism for impaired diastolic relaxation and stiffness in patients with heart failure with preserved ejection fraction (HFpEF) is the presence of coronary microvascular dysfunction (CMD). Invasive studies have demonstrated that HFpEF can be present in patients regardless of the presence or absence of echocardiographic diastolic dysfunction. Hypothesis: We hypothesize that CMD is common in HFpEF with normal and abnormal echocardiographic diastolic function. Methods: In a prospective study of HFpEF patients (n=30), clinical, echocardiographic, hemodynamic, and coronary physiology (CP) data were evaluated. CP parameters measured included coronary flow reserve (CFR) and index of microvascular resistance (IMR). Echocardiographic diastolic dysfunction (DD) was graded according to current ASE guidelines. Baseline clinical, echocardiographic, hemodynamic, and CP data were compared between grade 0 DD (n=10) and grade 1-3 DD (n=11), excluding patients with indeterminate DD grade (n=10). Results: Age, gender, and comorbidities were similar in the grade 0 compared to grade 1-3 DD groups. Median BNP was higher in the grade 1-3 compared to the grade 0 DD group (462 vs. 98, p=0.012). All DD and strain measurements were significantly abnormal in the grade 1-3 compared to grade 0 DD groups, as were mean pulmonary artery, and left-sided filling pressures. Mean IMR was elevated and similar in patients with and without DD (30.5 vs. 27.9, p=0.58), however mean CFR was abnormal and lower in the grade 1-3 compared to grade 0 DD groups (2.05 vs. 3.30, p=0.053). Conclusions: Although BNP, LV and left atrial strain, and LV filling pressures were higher in HFpEF patients with abnormal diastolic function compared to "normal" diastolic function, we found that elevated microvascular resistance is present in patients with HFpEF and "normal" diastolic function, but these patients have relatively preserved CFR.