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      Diagnostic Accuracy of Tissue Doppler Index E/è for Evaluating Left Ventricular Filling Pressure and Diastolic Dysfunction/Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta‐Analysis

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          Abstract

          Background

          Tissue Doppler index E/è is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure ( LVFP) and diastolic dysfunction ( DD)/heart failure with preserved ejection fraction ( HFp EF). Its diagnostic accuracy is not well studied.

          Methods and Results

          From the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/è and invasive LVFP in preserved EF (≥50%). In random‐effects models, E/è had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography–recommended E/è cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9–48%), 37% (13–61%), and 24% (6–46%), and summary specificity was 92% (82–100%), 91% (80–99%), and 98% (92–100%). Positive likelihood ratio ( LR+) was <5 for lateral and mean E/è. LR+ was slightly >10 for septal E/è obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/è (lateral, mean, and septal, respectively) was 64% (38–86%), 36% (3–74%), and 50% (14–81%), while summary specificity was 73% (54–89%), 83% (49–100%), and 89% (66–100%). Because of data set limitations, meaningful inference for identifying HFp EF by using E/è could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability.

          Conclusions

          There is insufficient evidence to support that E/è can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/è to identify/exclude elevated LVFP and DD/ HFp EF is limited and requires further validation in a well‐designed prospective clinical trial.

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          Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic.

          Margaret M. Redfield, Steven J Jacobsen, John C Burnett … (2003)
          Approximately half of patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (EF). Yet, the prevalence of diastolic dysfunction and its relation to systolic dysfunction and CHF in the community remain undefined. To determine the prevalence of CHF and preclinical diastolic dysfunction and systolic dysfunction in the community and determine if diastolic dysfunction is predictive of all-cause mortality. Cross-sectional survey of 2042 randomly selected residents of Olmsted County, Minnesota, aged 45 years or older from June 1997 through September 2000. Doppler echocardiographic assessment of systolic and diastolic function. Presence of CHF diagnosis by review of medical records with designation as validated CHF if Framingham criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or systolic dysfunction were considered as having either preclinical diastolic or preclinical systolic dysfunction. The prevalence of validated CHF was 2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than 50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and 0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%-6.7%) of the population having moderate or severe diastolic dysfunction with normal EF. The prevalence of any systolic dysfunction (EF < or =50%) was 6.0% (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF < or =40%) being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those with systolic or diastolic dysfunction than in those with normal ventricular function. However, even among those with moderate or severe diastolic or systolic dysfunction, less than half had recognized CHF. In multivariate analysis, controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31 [95% CI, 3.00-23.1], P<.001) and moderate or severe diastolic dysfunction (hazard ratio, 10.17 [95% CI, 3.28-31.0], P<.001) were predictive of all-cause mortality. In the community, systolic dysfunction is frequently present in individuals without recognized CHF. Furthermore, diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognized CHF, and associated with marked increases in all-cause mortality.
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            Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction.

            Barry Borlaug, Rick A. Nishimura, Paul Sorajja … (2010)
            When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest. Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP ≥25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater increases in left ventricular end-diastolic pressure and was associated with blunted increases in heart rate, systemic vasodilation, and cardiac output. Exercise-induced pulmonary hypertension was present in 88% of patients with HFpEF and was related principally to elevated PCWP, as pulmonary vascular resistances dropped similarly in both groups. Exercise PCWP and pulmonary artery systolic pressure were highly correlated. An exercise pulmonary artery systolic pressure ≥45 mm Hg identified HFpEF with 96% sensitivity and 95% specificity. Euvolemic patients with exertional dyspnea, normal brain natriuretic peptide, and normal cardiac filling pressures at rest may have markedly abnormal hemodynamic responses during exercise, suggesting that chronic symptoms are related to heart failure. Earlier and more accurate diagnosis using exercise hemodynamics may allow better targeting of interventions to treat and prevent HFpEF progression.
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              Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial.

              Frank Edelmann, Rolf Wachter, Albrecht G Schmidt … (2013)
              Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression. To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction. The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction. Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up. The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months. Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P < .001). Peak VO2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m2; 95% CI, -10 to-1 g/m2; P = .009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15 m; 95% CI, -27 to -2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P < .001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73 m2; 95% CI, -8 to -3 mL/min/1.73 m2; P < .001) without affecting hospitalizations. In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations. clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31.
              Article 0 comments Cited 195 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Am Heart Assoc
                Journal ID (iso-abbrev): J Am Heart Assoc
                Journal ID (doi): 10.1002/(ISSN)2047-9980
                Journal ID (publisher-id): JAH3
                Journal ID (hwp): ahaoa
                Title: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2047-9980
                Publication date (Electronic): 25 January 2016
                Publication date Collection: January 2016
                Volume: 5
                Issue: 1 ( doiID: 10.1002/jah3.2016.5.issue-1 )
                Electronic Location Identifier: e002530
                Affiliations
                [ 1 ] Department of MedicineUniversity of Alabama at Birmingham AL
                [ 2 ] Department of BiostatistcsUniversity of Alabama at Birmingham AL
                [ 3 ] Department of Electrical and Computer EngineeringAuburn University Auburn AL
                [ 4 ]VA Medical Center Birmingham AL
                Author notes
                [*] [* ] Correspondence to: Himanshu Gupta, MD, FACC, Medicine and Radiology, University of Alabama at Birmingham, BDB‐101, 1808 7th Avenue South, Birmingham, AL 35294‐0012. E‐mail: hgupta@ 123456uab.edu
                Article
                Publisher ID: JAH31280
                DOI: 10.1161/JAHA.115.002530
                PMC ID: 4859370
                PubMed ID: 26811160
                SO-VID: e87fa4eb-eab0-4ff9-8c96-d538b68c0c32
                Copyright © © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 07 August 2015
                Date accepted : 18 November 2015
                Page count
                Pages: 19
                Funding
                Funded by: National Institutes of Health
                Award ID: NHLBI R01‐HL104018
                Categories
                Subject: Original Research
                Subject: Original Research
                Subject: Heart Failure
                Custom metadata
                source-schema-version-number 2.0
                component-id jah31280
                cover-date January 2016
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.9 mode:remove_FC converted:04.05.2016

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: diagnostic accuracy,diastolic dysfunction,e/è,heart failure with preserved ejection fraction,left ventricular filling pressure,tissue doppler imaging,echocardiography,heart failure,diagnostic testing,meta analysis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: diagnostic accuracy, diastolic dysfunction, e/è, heart failure with preserved ejection fraction, left ventricular filling pressure, tissue doppler imaging, echocardiography, heart failure, diagnostic testing, meta analysis

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