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Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain.

ABSTRACT: Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, 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 or right ventricular longitudinal strain.We evaluated baseline LA function in 308 patients with HFpEF who were followed up longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of left ventricular longitudinal strain, right ventricular free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of left ventricular, right ventricular, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years, 64% were women, 26% had atrial fibrillation, and LA enlargement was present in the majority of patients (67%). Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the left ventricular, right ventricular, 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 hazard ratio per 1-SD decrease in LA strain, 1.54; 95% CI, 1.15-2.07; P=0.006).Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and augmentation of LA function may be important future therapeutic targets in HFpEF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.

SUBMITTER: Freed BH

PROVIDER: S-EPMC4780261 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain.

Freed Benjamin H BH Daruwalla Vistasp V Cheng Jeanette Y JY Aguilar Frank G FG Beussink Lauren L Choi Andrew A Klein David A DA Dixon Debra D Baldridge Abigail A Rasmussen-Torvik Laura J LJ Maganti Kameswari K Shah Sanjiv J SJ

Circulation. Cardiovascular imaging 20160301 3

<h4>Background</h4>Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, 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 or right ventricular longitudinal strain.<h4>Methods and results</h4>We evaluated baseline LA functio ...[more]

PMID: 26941415

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Project description:BackgroundImpairment of left atrial (LA) function is linked to left ventricle (LV) mechanics in patients with heart failure with preserved ejection fraction (HFpEF). In this study, we set forth to determine the difference in LA mechanics compared between HFpEF patients with different degrees of LV strains using the cardiac magnetic resonance feature tracking technique.MethodsThis retrospective study enrolled 79 patients with prior heart failure event and LV ejection fraction (LVEF) ≥ 50% (HFpEF group) together with 2:1 matched controls. LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS); LA emptying fraction (LAEF); and, LA strains consisting of reservoir phase strain (LASr), conduit phase strain (LAScd), and contraction phase strain (LASct) were derived from cine images. All LA parameters were compared between HFpEF subgroups (lower and higher LV strain stratified by the median of each LV strain value) and controls.ResultsA total of 237 subjects were included. HFpEF had a lower LAEF and LA strain values compared with controls. The mean GLS value was significantly different between HFpEF and controls (- 13.3 ± 3.4% vs. - 15.4 ± 2.2%, p < 0.001). HFpEF with lower GLS (value ≥ - 13.1%) had significantly impaired LA mechanical parameters compared with both HFpEF with higher GLS and controls independent of potential confounders, as follows: LAEF (38.8 ± 16.6% vs. 48.6 ± 15.7% and 54.2 ± 12.2%), LASr (14.6 ± 7.1% vs. 24.3 ± 9.6% and 26.7 ± 8.8%), and LAScd (- 6.6 ± 3.9% vs. - 12.9 ± 6.0% and - 14.7 ± 7.4%) (post hoc analysis of variance p < 0.05 for all comparisons). Similarly, HFpEF with lower GCS (value ≥ - 16.6%) or lower GRS (value < 27.9%) also had significant impairment of LASr and LAScd compared with the higher strain group and controls. Abnormal LAEF (< 50%) and abnormal LASr (< 23%) are independently associated with NYHA class ≥ II (Odds ratio [OR] 3.894 [95% CI 2.202-6.885] p < 0.001, adjusted OR 3.382 [1.791-6.389] p < 0.001 for abnormal LAEF; and OR 2.613 [1.497-4.562] p = 0.001, adjusted OR 2.064 [1.118-2.110] p = 0.021 for abnormal LASr).ConclusionsPatients with HFpEF were found to have impaired LV and LA mechanics. Abnormal LA mechanics was highly prevalent in HFpEF patients with lower LV strain and significantly associated with the symptomatic status of the patients.

Project description:BackgroundMany patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure.ObjectivesThis study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH).MethodsThe REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH).ResultsPatients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present.ConclusionsPatients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

Project description:BackgroundLeft atrial (LA) 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 resultsWe assessed LA function measured by speckle-tracking echocardiography in 357 patients with HFpEF 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 left ventricular (LV) hypertrophy, worse LV and right ventricular systolic function, and worse LV diastolic function. At a mean follow-up of 31 months (interquartile range, 18-43months), 91 patients (25.5%) experienced the primary composite end point of cardiovascular death, HF hospitalization, and aborted sudden death. Lower peak LA strain was associated with a higher risk of the composite end point (hazard ratio, 0.96 per unit of reduction in strain; 95% confidence interval, 0.94-0.99; P=0.009) and of HF hospitalization alone (hazard ratio, 0.95 per unit of reduction in strain; 95% confidence interval, 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.ConclusionsLA 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 explains the association between impaired LA function and higher risk of HF hospitalization in HFpEF.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Project description:AimsNone of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF.MethodsWe prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI).ResultsLA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level.ConclusionsBy adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.

Project description:Background Maximal left atrial (LA) volume is reported by most echocardiography laboratories and is associated with clinical outcomes in patients with heart failure (HF). Recent studies suggest that minimal LA volume may better reflect left ventricular filling pressure and may be more prognostic than maximal LA volume. This study assessed the prognostic value of indexed minimal LA volume (LAVImin) in patients with HF with preserved ejection fraction. Methods and Results We assessed the relationship of LAVImin with a primary composite end point of cardiovascular death, aborted cardiac death, or HF hospitalization in 347 patients with HF with preserved ejection fraction enrolled from the Americas region in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We compared LAVImin with indexed maximal LA volume with respect to their prognostic values. In addition, we assessed if LA functional parameters provide additional prognostic information over LAVImin. During a median follow-up of 2.5 years, 107 patients (31%) experienced a primary composite end point. LAVImin was associated with increased risk of a primary composite outcome (hazard ratio [HR], 1.35; 95% CI, 1.12-1.61) and HF hospitalization alone (HR, 1.42; 95% CI, 1.17-1.71) after adjusting for clinical confounders and ejection fraction. In contrast, indexed maximal LA volume was not related to the primary composite outcome, but related to HF alone (HR, 1.25; 95% CI, 1.02-1.54). In comparison with indexed maximal LA volume, LAVImin was significantly more prognostic for primary composite outcome (P for comparison=0.032). Both LA emptying fraction and LA strain were prognostic of primary outcome independent of LAVImin (all P<0.05). Conclusions In patients with HF with preserved ejection fraction, LAVImin was more predictive of cardiovascular outcome than indexed maximal LA volume, suggesting this measure may be more physiologically relevant and might better identify patients at high risk for cardiovascular events. LA functional parameters provide prognostic information independent of LAVImin. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00094302.

Project description:AimsTwo key echocardiographic parameters that are currently used to diagnose heart failure (HF) with preserved ejection fraction (HFpEF) are left atrial volume index (LAVi) and left ventricular mass index (LVMi). We investigated whether patients' characteristics, biomarkers, and co-morbidities are associated with these parameters and whether the relationships differ between patients with HFpEF or HF with reduced ejection fraction (HFrEF).MethodsWe consecutively enrolled 831 outpatients with typical signs and symptoms of HF and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels and categorized patients based upon left ventricular ejection fraction (LVEF): LVEF < 40% (HFrEF), LVEF between 40% and 50% (HF with mid-range ejection fraction), and LVEF ≥ 50% (HFpEF). The study includes consecutively enrolled HF patients from an HF outpatient clinic at a tertiary medical centre in the Netherlands. All patients underwent baseline characterization, laboratory measurements, and echocardiography.ResultsFour hundred sixty-nine patients had HFrEF, 189 HF with mid-range ejection fraction, and 173 HFpEF. The patients with HFrEF were rather male [HFrEF: 323 (69%); HFpEF: 80 (46%); P < 0.001], and the age was comparable (HFrEF 67 ± 13; HFpEF 70 ± 14; P = 0.069). In HFpEF, more patients had hypertension [190 (40.5%); 114 (65.9%); P < 0.001], higher body mass indices (27 ± 8; 30 ± 7; P < 0.001), and atrial fibrillation [194 (41.4); 86 (49.7); P = 0.029]. The correlation analyses showed that in HFrEF patients, LAVi was significantly associated with age (β 0.293; P < 0.001), male gender (β 0.104; P = 0.042), body mass index (β -0160; P = 0.002), diastolic blood pressure (β -0.136; P < 0.001), New York Heart Association (β 0.174; P = 0.001), atrial fibrillation (β 0.381; P < 0.001), galectin 3 (β 0.230; P < 0.001), NT-proBNP (β 0.183; P < 0.001), estimated glomerular filtration rate (β -0.205; P < 0.001), LVEF (β -0.173; P = 0.001), and LVMi (β 0.337; P < 0.001). In HFpEF patients, only age (β 0.326; P < 0.001), atrial fibrillation (β 0.386; P < 0.001), NT-proBNP (β 0.176; P = 0.036), and LVMi (β 0.213; P = 0.013) were associated with LAVi.ConclusionsAlthough LVMi and LAVi are hallmark parameters to diagnose HFpEF, they only correlate with a few characteristics of HF and mainly with atrial fibrillation. In contrast, in HFrEF patients, LAVi relates strongly to several other HF parameters. These findings underscore the complexity in visualizing the pathophysiology of HFpEF and question the relation between cardiac structural remodeling and the impact of co-morbidities.

Dataset Information

Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain.

Publications

Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain.

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