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      Hemodynamic force assessment by cardiovascular magnetic resonance in HFpEF: A case-control substudy from the HFpEF stress trial

      research-article
      Author(s): a , b , c , a , a , b , a , b , a , b , c , a , b , a , b , a , b , c , ∗
      Publication date (Electronic):
      Journal: eBioMedicine
      Publisher: Elsevier
      Keywords: HFpEF, Cardiovascular magnetic resonance, Hemodynamic force, Deformation imaging, Strain, AUC, area under the curve, bSSFP, balanced steady state free precession, CI, confidence intervals, CMR, cardiovascular magnetic resonance, CV, chamber view, CVH, cardiovascular hospitalisation, GLS/GCS/GRS, global longitudinal/circumferential/radial strain, EDV/ESV, End diastolic/systolic volume, Ees, End-systolic elastance, EF, Ejection fraction, FT, Feature tracking, HDF, hemodynamic force, HFpEF, heart failure with preserved ejection fraction, HFrEF, heart failure with reduced ejection fraction, HR, hazard ratio, IQR, interquartile ranges, IVPG, intraventricular pressure gradient, LV, Left ventricular, LAS, Long axis strain, LAVI, Left atrial volume index, LAX, Long axis, NCD, Non cardiac dyspnoea, NTproBNP, N-terminal prohormone of brain natriuretic peptide, NYHA, New York Heart Association, PCWP, Pulmonary capillary wedge pressure, PVL, Pressure volume loops, RHC, right heart catheterisation, RMS, Root mean square, RV, Right ventricular, SAX, Short axis, SV, Stroke volume

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          Summary

          Background

          The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Exercise-stress testing is recommended in case of uncertainty; however, this approach is time-consuming and costly. Since preserved EF does not represent normal systolic function, we hypothesized comprehensive cardiovascular magnetic resonance (CMR) assessment of cardiac hemodynamic forces (HDF) may identify functional abnormalities in HFpEF.

          Methods

          The HFpEF Stress Trial (DZHK-17; Clinicaltrials.gov: NCT03260621) prospectively recruited 75 patients with exertional dyspnea, preserved EF (≥50%) and signs of diastolic dysfunction (E/e’ ≥8) on echocardiography. Patients underwent rest and exercise-stress right heart catheterisation, echocardiography and CMR. The final study cohort consisted of 68 patients (HFpEF n = 34 and non-cardiac dyspnea n = 34 according to pulmonary capillary wedge pressure (PCWP)). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, E-wave deceleration as well as A-wave acceleration forces. Follow-up after 24 months evaluated cardiovascular mortality and hospitalisation (CVH) – only two patients were lost to follow-up.

          Findings

          HDF assessment revealed impairment of LV longitudinal function in patients with HFpEF compared to non-cardiac dyspnoea (15.8% vs. 18.3%, p = 0.035), attributable to impairment of systolic peak (38.6% vs 51.6%, p = 0.003) and impulse (20.8% vs. 24.5%, p = 0.009) forces as well as late diastolic filling (−3.8% vs −5.4%, p = 0.029). Early diastolic filling was impaired in HFpEF patients identified at rest compared with patients identified during stress only (7.7% vs. 9.9%, p = 0.004). Impaired systolic peak was associated with CVH (HR 0.95, p = 0.016), and was superior to LV global longitudinal strain assessment in prediction of CVH (AUC 0.76 vs. 0.61, p = 0.048).

          Interpretation

          Assessment of HDF indicates impairment of LV systolic ejection force in HFpEF which is associated with cardiovascular events.

          Funding

          doi 10.13039/100010147, German Centre for Cardiovascular Research (DZHK); .

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          Most cited references45

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          Empagliflozin in Heart Failure with a Preserved Ejection Fraction

          Stefan D. Anker, Javed Butler, Gerasimos Filippatos … (2022)
          Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.
          Article 0 comments Cited 1228 times – based on 0 reviews     Review now
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            Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.

            E R DeLong, D M Delong, D Clarke-Pearson (1988)
            Methods of evaluating and comparing the performance of diagnostic tests are of increasing importance as new tests are developed and marketed. When a test is based on an observed variable that lies on a continuous or graded scale, an assessment of the overall value of the test can be made through the use of a receiver operating characteristic (ROC) curve. The curve is constructed by varying the cutpoint used to determine which values of the observed variable will be considered abnormal and then plotting the resulting sensitivities against the corresponding false positive rates. When two or more empirical curves are constructed based on tests performed on the same individuals, statistical analysis on differences between curves must take into account the correlated nature of the data. This paper presents a nonparametric approach to the analysis of areas under correlated ROC curves, by using the theory on generalized U-statistics to generate an estimated covariance matrix.
            Article 0 comments Cited 681 times – based on 0 reviews     Review now
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              Spironolactone for heart failure with preserved ejection fraction.

              Bertram Pitt, Marc Pfeffer, Susan Assmann … (2014)
              Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).
              Article 0 comments Cited 508 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Andreas Schuster
                Journal
                Journal ID (nlm-ta): eBioMedicine
                Journal ID (iso-abbrev): EBioMedicine
                Title: eBioMedicine
                Publisher: Elsevier
                ISSN (Electronic): 2352-3964
                Publication date PMC-release: 21 November 2022
                Publication date Collection: December 2022
                Publication date (Electronic): 21 November 2022
                Volume: 86
                Electronic Location Identifier: 104334
                Affiliations
                [a ]University Medical Center Göttingen, Department of Cardiology and Pneumology, Georg-August University, Göttingen, Germany
                [b ]German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
                [c ]School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom
                Author notes
                [∗ ]Corresponding author. University Medical Centre, Georg-August-University Göttingen, Department of Cardiology and Pneumology, Robert-Koch-Str. 40, 37099, Göttingen, Germany. andreas_schuster@ 123456gmx.net
                Article
                Publisher Item ID: S2352-3964(22)00516-3 Publisher ID: 104334
                DOI: 10.1016/j.ebiom.2022.104334
                PMC ID: 9691873
                PubMed ID: 36423376
                SO-VID: ad8257be-fb64-404e-94b8-fe4510ddaf0e
                Copyright © © 2022 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 23 May 2022
                Date revision received : 15 October 2022
                Date accepted : 17 October 2022
                Categories
                Subject: Articles

                Keywords: hfpef,cardiovascular magnetic resonance,hemodynamic force,deformation imaging,strain,auc, area under the curve,bssfp, balanced steady state free precession,ci, confidence intervals,cmr, cardiovascular magnetic resonance,cv, chamber view,cvh, cardiovascular hospitalisation,gls/gcs/grs, global longitudinal/circumferential/radial strain,edv/esv, end diastolic/systolic volume,ees, end-systolic elastance,ef, ejection fraction,ft, feature tracking,hdf, hemodynamic force,hfpef, heart failure with preserved ejection fraction,hfref, heart failure with reduced ejection fraction,hr, hazard ratio,iqr, interquartile ranges,ivpg, intraventricular pressure gradient,lv, left ventricular,las, long axis strain,lavi, left atrial volume index,lax, long axis,ncd, non cardiac dyspnoea,ntprobnp, n-terminal prohormone of brain natriuretic peptide,nyha, new york heart association,pcwp, pulmonary capillary wedge pressure,pvl, pressure volume loops,rhc, right heart catheterisation,rms, root mean square,rv, right ventricular,sax, short axis,sv, stroke volume
                Data availability:
                Keywords: hfpef, cardiovascular magnetic resonance, hemodynamic force, deformation imaging, strain, auc, area under the curve, bssfp, balanced steady state free precession, ci, confidence intervals, cmr, cardiovascular magnetic resonance, cv, chamber view, cvh, cardiovascular hospitalisation, gls/gcs/grs, global longitudinal/circumferential/radial strain, edv/esv, end diastolic/systolic volume, ees, end-systolic elastance, ef, ejection fraction, ft, feature tracking, hdf, hemodynamic force, hfpef, heart failure with preserved ejection fraction, hfref, heart failure with reduced ejection fraction, hr, hazard ratio, iqr, interquartile ranges, ivpg, intraventricular pressure gradient, lv, left ventricular, las, long axis strain, lavi, left atrial volume index, lax, long axis, ncd, non cardiac dyspnoea, ntprobnp, n-terminal prohormone of brain natriuretic peptide, nyha, new york heart association, pcwp, pulmonary capillary wedge pressure, pvl, pressure volume loops, rhc, right heart catheterisation, rms, root mean square, rv, right ventricular, sax, short axis, sv, stroke volume

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