6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Impact of Sex on Ventricular‐Vascular Stiffness and Long‐Term Outcomes in Heart Failure With Preserved Ejection Fraction: TOPCAT Trial Substudy

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Women have higher vascular stiffness with aging. The aim of this study was to characterize sex differences in vascular and ventricular structure and function, and to investigate the impact on the primary outcome in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial).

          Methods and Results

          Data from the Americas cohort of the TOPCAT trial were analyzed. Patients with echocardiography (n=654) were compared according to sex, and achievement of the primary end point (a composite of death from cardiovascular causes and heart failure hospitalization) assessed. Echocardiography revealed higher arterial, systolic, and diastolic ventricular elastance and worse ventricular‐vascular coupling in women. Women had better overall survival and heart failure hospitalization outcomes (hazard ratio 0.74, 95% CI 0.57–0.98, P=0.034), however, determinants of achievement of the primary outcome differed between the sexes. Pulse pressure was a key determinant of outcome in women (hazard ratio 1.04, 95% CI 1–1.09, P=0.034) whereas in men heart rate (hazard ratio 1.61, 95% CI 1.02–2.52 per 10 mm Hg increase, P=0.04) and B‐type natriuretic peptide (hazard ratio 1.01, 95% CI 1–1.02 per 10 ng/mL increase P=0.02) were associated with poorer outcome.

          Conclusions

          Outcomes in patients with heart failure with preserved ejection fraction appear to be differentially influenced by key physiological factors that vary according to sex. In women, ventricular‐vascular stiffening was the most significant determinant of outcome, whereas in men overall survival was influenced by heart rate and B‐type natriuretic peptide; this highlights key sex differences in the pathophysiology and outcomes of heart failure with preserved ejection fraction and warrants further exploration.

          Clinical Trial Registration

          URL: https://clinicaltrials.gov. Unique identifier: NCT00094302.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial.

          Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas).
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Heart failure with preserved ejection fraction: from mechanisms to therapies

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota.

              Mechanisms purported to contribute to the pathophysiology of heart failure with normal ejection fraction (HFnlEF) include diastolic dysfunction, vascular and left ventricular systolic stiffening, and volume expansion. We characterized left ventricular volume, effective arterial elastance, left ventricular end-systolic elastance, and left ventricular diastolic elastance and relaxation noninvasively in consecutive HFnlEF patients and appropriate controls in the community. Olmsted County (Minn) residents without cardiovascular disease (n=617), with hypertension but no heart failure (n=719), or with HFnlEF (n=244) were prospectively enrolled. End-diastolic volume index was determined by echo Doppler. End-systolic elastance was determined using blood pressure, stroke volume, ejection fraction, timing intervals, and estimated normalized ventricular elastance at end diastole. Tissue Doppler e' velocity was used to estimate the time constant of relaxation. End-diastolic volume (EDV) and Doppler-derived end-diastolic pressure (EDP) were used to derive the diastolic curve fitting (alpha) and stiffness (beta) constants (EDP=alphaEDVbeta). Comparisons were adjusted for age, sex, and body size. HFnlEF patients had more severe renal dysfunction, yet smaller end-diastolic volume index and cardiac output and increased EDP compared with both hypertensive and healthy controls. Arterial elastance and ventricular end-systolic elastance were similarly increased in hypertensive controls and HFnlEF patients compared with healthy controls. In contrast, HFnlEF patients had more impaired relaxation and increased diastolic stiffness compared with either control group. From these cross-sectional observations, we speculate that the progression of diastolic dysfunction plays a key role in the development of heart failure symptoms in persons with hypertensive heart disease.
                Bookmark

                Author and article information

                Contributors
                david.kaye@baker.edu.au
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                22 June 2019
                02 July 2019
                : 8
                : 13 ( doiID: 10.1002/jah3.2019.8.issue-13 )
                : e012190
                Affiliations
                [ 1 ] Department of Cardiology Alfred Hospital Melbourne Australia
                [ 2 ] Heart Failure Research Group Baker Heart and Diabetes Institute Melbourne Australia
                [ 3 ] Department of Medicine Monash University Melbourne Australia
                Author notes
                [*] [* ] Correspondence to: David M. Kaye, MBBS, PhD, Department of Cardiology, Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia. E‐mail: david.kaye@ 123456baker.edu.au
                Article
                JAH34189
                10.1161/JAHA.119.012190
                6662372
                31230508
                849f78c3-bba9-47d6-be15-7481ca2a13de
                © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 31 January 2019
                : 17 May 2019
                Page count
                Figures: 2, Tables: 3, Pages: 8, Words: 6590
                Categories
                Original Research
                Original Research
                Heart Failure
                Custom metadata
                2.0
                jah34189
                02 July 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.6.2 mode:remove_FC converted:23.07.2019

                Cardiovascular Medicine
                health outcomes,heart failure,pulse pressure,sex differences,mortality/survival,vascular disease

                Comments

                Comment on this article