Research Article| Volume 190, P17-24, March 01, 2023

Hemodynamic Gain Index and Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Published:December 20, 2022DOI:
      Decreased exercise capacity portends a poor prognosis in heart failure with preserved ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker of hemodynamic reserve measured during exercise stress testing and is associated with survival. The goal of this study was to establish the association of HGI with exercise capacity, serum biomarkers, and echocardiography features in subjects with HFpEF. In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate [HR] × peak systolic blood pressure [SBP]–[HR at rest × SBP at rest])/(HR at rest × SBP at rest) and tested associations with outcomes of interest. The median (interquartile range) HGI was 0.94 (0.5 to 1.3) beats per min/mm Hg. In multivariable-adjusted linear regression, higher HGI was associated with greater peak oxygen consumption (VO2), VO2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all p <0.001). Higher HGI was associated with lower serum high-sensitivity troponin I, pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p <0.05) and with longer deceleration time, lower E/A ratio, and lower left atrial volume index by echocardiography (all p <0.05). In conclusion, higher HGI in stable HFpEF was associated with greater exercise capacity, a biomarker profile indicating less myocardial injury and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction. These results suggest that HGI, an easily calculated metric from routine exercise testing, is a marker of functional capacity and disease severity in HFpEF and may serve as a surrogate for VO2 parameters for use in treadmill testing without gas exchange capability.
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        • Salzano A
        • De Luca M
        • Israr MZ
        • Crisci G
        • Eltayeb M
        • Debiec R
        • Ranieri B
        • D'Assante R
        • Rega S
        • D'Agostino A
        • Mauro C
        • Squire IB
        • Suzuki T
        • Bossone E
        • Guazzi M
        • Marra AM
        Exercise intolerance in heart failure with preserved ejection fraction.
        Heart Fail Clin. 2021; 17: 397-413
        • Guazzi M
        • Myers J
        • Arena R.
        Cardiopulmonary exercise testing in the clinical and prognostic assessment of diastolic heart failure.
        J Am Coll Cardiol. 2005; 46: 1883-1890
        • Guazzi M
        • Myers J
        • Peberdy MA
        • Bensimhon D
        • Chase P
        • Arena R.
        Exercise oscillatory breathing in diastolic heart failure: prevalence and prognostic insights.
        Eur Heart J. 2008; 29: 2751-2759
        • Yan J
        • Gong SJ
        • Li L
        • Yu HY
        • Dai HW
        • Chen J
        • Tan CW
        • Xv QH
        • Cai GL.
        Combination of B-type natriuretic peptide and minute ventilation/carbon dioxide production slope improves risk stratification in patients with diastolic heart failure.
        Int J Cardiol. 2013; 162: 193-198
        • Shafiq A
        • Brawner CA
        • Aldred HA
        • Lewis B
        • Williams CT
        • Tita C
        • Schairer JR
        • Ehrman JK
        • Velez M
        • Selektor Y
        • Lanfear DE
        • Keteyian SJ.
        Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal cardiopulmonary exercise testing (FIT-CPX) project.
        Am Heart J. 2016; 174: 167-172
        • Nadruz Jr, W
        • West E
        • Sengeløv M
        • Santos M
        • Groarke JD
        • Forman DE
        • Claggett B
        • Skali H
        • Shah AM.
        Prognostic value of cardiopulmonary exercise testing in heart failure with reduced, midrange, and preserved ejection fraction.
        J Am Heart Assoc. 2017; 6e006000
        • Pandey A
        • Parashar A
        • Kumbhani D
        • Agarwal S
        • Garg J
        • Kitzman D
        • Levine B
        • Drazner M
        • Berry J.
        Exercise training in patients with heart failure and preserved ejection fraction: meta-analysis of randomized control trials.
        Circ Heart Fail. 2015; 8: 33-40
        • Leggio M
        • Fusco A
        • Loreti C
        • Limongelli G
        • Bendini MG
        • Mazza A
        • Coraci D
        • Padua L.
        Effects of exercise training in heart failure with preserved ejection fraction: an updated systematic literature review.
        Heart Fail Rev. 2020; 25: 703-711
        • Vainshelboim B
        • Kokkinos P
        • Myers J.
        Prognostic value and clinical usefulness of the hemodynamic gain index in men.
        Am J Cardiol. 2019; 124: 644-649
        • Vainshelboim B
        • Kokkinos P
        • Myers J.
        Hemodynamic gain index in women: a validation study.
        Int J Cardiol. 2020; 308: 15-19
        • Redfield MM
        • Chen HH
        • Borlaug BA
        • Semigran MJ
        • Lee KL
        • Lewis G
        • LeWinter MM
        • Rouleau JL
        • Bull DA
        • Mann DL
        • Deswal A
        • Stevenson LW
        • Givertz MM
        • Ofili EO
        • O'Connor CM
        • Felker GM
        • Goldsmith SR
        • Bart BA
        • McNulty SE
        • Ibarra JC
        • Lin G
        • Oh JK
        • Patel MR
        • Kim RJ
        • Tracy RP
        • Velazquez EJ
        • Anstrom KJ
        • Hernandez AF
        • Mascette AM
        • Braunwald E
        • RELAX Trial
        Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.
        JAMA. 2013; 309: 1268-1277
        • Redfield MM
        • Borlaug BA
        • Lewis GD
        • Mohammed SF
        • Semigran MJ
        • LeWinter MM
        • Deswal A
        • Hernandez AF
        • Lee KL
        • Braunwald E
        • Heart Failure Clinical Research Network
        PhosphdiesteRasE-5 inhibition to improve cLinical status and eXercise capacity in diastolic heart failure (RELAX) trial: rationale and design.
        Circ Heart Fail. 2012; 5: 653-659
        • Porszasz J
        • Casaburi R
        • Somfay A
        • Woodhouse LJ
        • Whipp BJ.
        A treadmill ramp protocol using simultaneous changes in speed and grade.
        Med Sci Sports Exerc. 2003; 35: 1596-1603
        • Malhotra R
        • Bakken K
        • D'Elia E
        • Lewis GD
        Cardiopulmonary exercise testing in heart failure.
        JACC Heart Fail. 2016; 4: 607-616
        • Youn JC
        • Ahn Y
        • Jung HO
        Pathophysiology of heart failure with preserved ejection fraction.
        Heart Fail Clin. 2021; 17: 327-335
        • Borlaug BA
        • Melenovsky V
        • Russell SD
        • Kessler K
        • Pacak K
        • Becker LC
        • Kass DA
        Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.
        Circulation. 2006; 114: 2138-2147
        • Borlaug BA
        • Kane GC
        • Melenovsky V
        • Olson TP.
        Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction.
        Eur Heart J. 2016; 37: 3293-3302
        • Borlaug BA
        • Olson TP
        • Lam CS
        • Flood KS
        • Lerman A
        • Johnson BD
        • Redfield MM.
        Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction.
        J Am Coll Cardiol. 2010; 56: 845-854
        • Unger ED
        • Dubin RF
        • Deo R
        • Daruwalla V
        • Friedman JL
        • Medina C
        • Beussink L
        • Freed BH
        • Shah SJ.
        Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.
        Eur J Heart Fail. 2016; 18: 103-112
        • Yancy CW
        • Jessup M
        • Bozkurt B
        • Butler J
        • Casey Jr, DE
        • Colvin MM
        • Drazner MH
        • Filippatos GS
        • Fonarow GC
        • Givertz MM
        • Hollenberg SM
        • Lindenfeld J
        • Masoudi FA
        • McBride PE
        • Peterson PN
        • Stevenson LW
        • Westlake C
        2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America.
        Circulation. 2017; 136: e137-e161
        • Gohar A
        • Chong JPC
        • Liew OW
        • den Ruijter H
        • de Kleijn DPV
        • Sim D
        • Yeo DPS
        • Ong HY
        • Jaufeerally F
        • Leong GKT
        • Ling LH
        • Lam CSP
        • Richards AM.
        The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction.
        Eur J Heart Fail. 2017; 19: 1638-1647
        • Carnes J
        • Gordon G.
        Biomarkers in heart failure with preserved ejection fraction: an update on progress and future challenges.
        Heart Lung Circ. 2020; 29: 62-68
        • Duprez DA
        • Gross MD
        • Kizer JR
        • Ix JH
        • Hundley WG
        • Jacobs Jr., DR
        Predictive value of collagen biomarkers for heart failure with and without preserved ejection fraction: MESA (Multi-Ethnic Study of Atherosclerosis).
        J Am Heart Assoc. 2018; 7e007885
        • Zile MR
        • DeSantis SM
        • Baicu CF
        • Stroud RE
        • Thompson SB
        • McClure CD
        • Mehurg SM
        • Spinale FG.
        Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure.
        Circ Heart Fail. 2011; 4: 246-256
        • Zile MR
        • Jhund PS
        • Baicu CF
        • Claggett BL
        • Pieske B
        • Voors AA
        • Prescott MF
        • Shi V
        • Lefkowitz M
        • McMurray JJ
        • Solomon SD
        • Prospective Comparison of ARNI with ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators
        Plasma biomarkers reflecting profibrotic processes in heart failure with a preserved ejection fraction: data from the prospective comparison of ARNI with ARB on management of heart failure with preserved ejection fraction study.
        Circ Heart Fail. 2016; 9e002551
        • Todd N
        • Lai YC.
        Current understanding of circulating biomarkers in pulmonary hypertension due to left heart disease.
        Front Med (Lausanne). 2020; 7570016