Peak O2 -pulse predicts exercise training-induced changes in peak V̇O2 in heart failure with preserved ejection fraction.

AIMS: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O2 ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O2 -pulse (V̇O2  × HR-1 , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O2 , is inversely associated with the change in peak V̇O2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. METHODS AND RESULTS: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O2 (%) was analysed as a function of baseline peak V̇O2 and its determinants (absolute peak V̇O2 , peak O2 -pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O2 through changes in peak O2 -pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O2 -pulse explained approximately 72% of the difference in changes in peak V̇O2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O2 -pulse on change in peak V̇O2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O2 -pulse was associated with a decreased mean change in peak V̇O2 of -1.45% (95% CI, -2.30 to -0.60, P = 0.001) compared with a mean change of -0.08% (95% CI, -1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O2 (P > 0.05). Change in V̇O2 at VT1 was not associated with any of the investigated factors (P > 0.05). CONCLUSIONS: In patients with HFpEF, the easily measurable peak O2 -pulse seems to be a good indicator of the potential for improving peak V̇O2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O2 -pulse, patients with high O2 -pulse may need to use additional therapies to significantly increase peak V̇O2 .

Potential usefulness and clinical relevance of a novel left atrial filling index to estimate left ventricular filling pressures in patients with preserved left ventricular ejection fraction.

AIMS: The aim of this study was to examine the potential usefulness and clinical relevance of a novel left atrial (LA) filling index using 2D speckle-tracking transthoracic echocardiography to estimate left ventricular (LV) filling pressures in patients with preserved LV ejection fraction (LVEF). METHODS AND RESULTS: The LA filling index was calculated as the ratio of the mitral early-diastolic inflow peak velocity (E) over LA reservoir strain (i.e. E/LA strain ratio). This index showed a good diagnostic performance to determine elevated LV filling pressures in a test-cohort (n = 31) using invasive measurements of LV end-diastolic pressure (area under the curve 0.82, cut-off > 3.27 = sensitivity 83.3%, specificity 78.9%), which was confirmed in a validation-cohort (patients with cardiovascular risk factors; n = 486) using the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging criteria (cut-off > 3.27 = sensitivity 88.1%, specificity 77.6%) and in a specificity-validation cohort (patients free of cardiovascular risk factors, n = 120; cut-off > 3.27 = specificity 98.3%). Regarding the clinical relevance of the LA filling index, an elevated E/LA strain ratio (>3.27) was significantly associated with the risk of heart failure hospitalization at 2 years (odds ratio 4.3, 95% confidence interval 1.8-10.5), even adjusting this analysis by age, sex, renal failure, LV hypertrophy, or abnormal LV global longitudinal systolic strain. CONCLUSION: The findings from this study suggest that a novel LA filling index using 2D speckle-tracking echocardiography could be of potential usefulness and clinical relevance in estimating LV filling pressures in patients with preserved LVEF.

Early detection of cardiac alterations by left atrial strain in patients with risk for cardiac abnormalities with preserved left ventricular systolic and diastolic function.

This study sought to examine whether early cardiac alterations could be detected by left atrial (LA) strain in patients with risk for cardiac abnormalities. In this cross-sectional and retrospective study, we included patients with (n = 234) and without (n = 48) risk for cardiac abnormalities (i.e. those with arterial hypertension, diabetes mellitus and/or a history of coronary artery disease) of similar age and with preserved left ventricular (LV) systolic and diastolic function according to standard criteria. LA strain was significantly altered in patients with risk for cardiac abnormalities in comparison to those without risk (29.2 ± 8.6 vs. 38.5 ± 12.6%; rate of impaired LA strain: 18.8% vs. 0%; all p < 0.01) and was the most sensitive parameter to detect early LA alterations in comparison with other LA functional parameters (rate of impaired LA strain rate, LA total emptying fraction, and LA expansion index 3.8%, 7.3%, and 3.8%, respectively). Moreover, in patients with risk for cardiac abnormalities LA strain was altered even in the absence of subtle LV systolic and diastolic alterations (rates 13.9% and 6.8%), albeit to a lesser extent than in patients with an abnormal LV longitudinal systolic strain or abnormal mitral annular e' velocities (rates 48.5% and 24.4%). Regarding the clinical relevance of these findings, an impaired LA strain (i.e. < 23%) was significantly linked to exertional dyspnea (OR 3.5 [1.7-7.0]) even adjusting the analyses by age, gender and subtle LV abnormalities. In conclusion, the findings from this study suggest that LA strain measurements could be useful to detect early cardiac alterations in patients with risk for cardiac abnormalities with preserved LV systolic and diastolic function and that these early LA strain alterations could be linked to exertional dyspnea.

Lower limit of normality and clinical relevance of left ventricular early diastolic strain rate for the detection of left ventricular diastolic dysfunction.

Aims: The aim of the present study was to determine the lower limit of normality and the clinical relevance of left ventricular (LV) early diastolic strain rate (LVSRe) for the detection of LV diastolic dysfunction (LVDD). Methods and results: Using 2D speckle-tracking echocardiography, we analysed 377 healthy subjects and 475 patients with risk for LVDD with preserved LV ejection fraction (LVEF). The normal range of LVSRe analysing the healthy subjects was 1.56 ± 0.28 s-1, with a lower limit of normality at 1.00 s-1. Using this cut-off, LVSRe was able to detect high rates of LV diastolic alterations (rate 71.1%), which was significantly better than using indirect diastolic parameters such as left atrial volume index (LAVI) and tricuspid regurgitation velocity (TR) (rates 22.9% and 9.1%) and similar to annular mitral parameters such as lateral and septal e' velocity (rates 70.9% and 72.4%). In line, adding LVSRe to the current evaluation of LVDD increased significantly the rate of detection of LVDD (absolute rate of increase 18.9%; rate of detection of LVDD: from 14.3% to 33.2%, P < 0.01). Regarding the clinical relevance of LVSRe, patients with abnormal LVSRe (i.e. <1.00 s-1) had significantly worse New York Heart Association functional class and symptomatic status than those with normal LVSRe. In addition, in a retrospective post hoc analysis, we found that an abnormal LVSRe had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio 5.0, 95% confidence interval 1.3-18.4), which was better than using conventional diastolic parameters such as septal and lateral e' velocity, LAVI and TR velocity. Conclusion: The findings from this multicentre study provide important data regarding the normal range of LVSRe and highlight the potential clinical relevance of using this new diastolic parameter in the detection of LVDD in patients with preserved LVEF.

Potential Usefulness and Clinical Relevance of Adding Left Atrial Strain to Left Atrial Volume Index in the Detection of Left Ventricular Diastolic Dysfunction.

OBJECTIVES: The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF). BACKGROUND: Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain. METHODS: Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF. RESULTS: In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p < 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p < 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., <23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 [95% confidence interval: 2.6 to 16.6]) even adjusting this analysis for age and sex and in patients with normal LAVI. CONCLUSIONS: The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF.

Left ventricular longitudinal systolic function analysed by 2D speckle-tracking echocardiography in heart failure with preserved ejection fraction: a meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to confirm if the global longitudinal systolic function of the left ventricle (LV) is altered in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We searched in different databases (Medline, Embase and Cochrane) studies that analysed LV global longitudinal systolic strain (GLS) in patients with HFpEF and in controls (such as healthy subjects or asymptomatic patients with arterial hypertension, diabetes mellitus or coronary artery disease). RESULTS: Twenty-two studies (2284 patients with HFpEF and 2302 controls) were included in the final analysis. Patients with HFpEF had significantly lower GLS than healthy subjects (mean -15.7% (range -12% to -18.9%) vs mean -19.9% (range -17.1% to -21.5%), weighted mean difference -4.2% (95% CI -3.3% to -5.0%), p < 0.001, respectively). In addition, patients with HFpEF had also significantly lower GLS than asymptomatic patients (mean -15.5% (range -13.4% to -18.4%) vs mean -18.3% (range -15.1% to -20.4%), weighted mean difference -2.8%(95% CI -1.9% to -3.6%), p < 0.001, respectively). In line, 10 studies showed that the rate of abnormal GLS was significantly higher in patients with HFpEF (mean 65.4% (range 37%-95%)) than in asymptomatic subjects (mean 13% (range 0%-29.6%)). Regarding the prognostic relevance of abnormal GLS in HFpEF, two multicentre studies with large sample size (447 and 348) and high number of events (115 and 177) showed that patients with abnormal GLS had worse cardiovascular (CV) outcomes than those with normal GLS (HR for CV mortality and HF hospitalisation 2.14 (95% CI 1.26 to 3.66) and 1.94 (95% CI 1.22 to 3.07)), even adjusting these analyses for multiples clinical and echocardiographic variables. CONCLUSION: The present meta-analysis analysing 2284 patients with HFpEF and 2302 controls confirms that the longitudinal systolic function of the LV is significantly altered in high proportion of patients with HFpEF. Further large multicentre studies with the aim to confirm the prognostic role of abnormal GLS in HFpEF are warranted.