Research Article|Articles in Press

Exertional Cardiac and Pulmonary Vascular Hemodynamics Among Patients with Heart Failure with Reduced Ejection Fraction

      Bullet points

      • Quantitative data regarding impact of exercise hemodynamic on functional capacity among patients with heart failure with reduced ejection fraction are lacking.
      • HFrEF patients experience marked increases in right- and left-sided filling pressures, as well as pul arterial pressures, during exercise, in addition to abnormal ventilatory parameters of exercise.



      Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF) but quantitative data regarding exertional hemodynamics are lacking.


      Characterize exertional cardiopulmonary hemodynamics in patients with HFrEF.


      Thirty-five HFrEF patients (59±12 years, 30 males) completed invasive cardiopulmonary exercise testing (CPET). Data were collected at rest, submaximal exercise and peak effort on upright cycle ergometry. Cardiovascular and pulmonary vascular hemodynamics were recorded. Fick cardiac output (Qc) was determined. Hemodynamic predictors of peak oxygen uptake (VO2) were identified.


      Left ventricular ejection fraction and cardiac index were 23±8% and 2.9±1.1 L/min/m2, respectively. PeakVO2 was 11.8±3.3 ml/kg/min and ventilatory efficiency slope was 53±13. Right atrial pressure increased from rest to peak exercise (4±5 v. 7±6mmHg,). Mean pulmonary arterial pressure increased from rest to peak exercise (27±13 v. 38±14mmHg). Pulmonary artery pulsatility index increased from rest to peak exercise, while pulmonary arterial capacitance and pulmonary vascular resistance declined.


      HFrEF patients suffer from marked increases in filling pressures during exercise. These findings provide new insight into cardiopulmonary abnormalities contributing to impairments in exercise capacity in this population.

      Clinical Trial Registration identifier: NCT03078972

      Lay Summary

      Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF). In this analysis, resting and exertional hemodynamics are analyzed from a contemporary cohort of patients with HFrEF (59±12 years, left ventricular ejection fraction 23±8%) during invasive cardiopulmonary exercise testing with upright cycle ergometry. During submaximal and peak exercise, large increases in left- and right-sided filling pressures were demonstrated. Maximal oxygen uptake was severely reduced and ventilatory efficiency was severely elevated. Multiple pulmonary vascular and right-sided hemodynamic parameters were predictive of functional capacity.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cardiac Failure
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Schwinger RHG
        • Bohm M
        • Koch A
        • et al.
        The Failing Human Heart is Unable to Use the Frank-Starling Mechanism.
        Circulation Research. 1994; 74: 959-969
        • Barrett-O'Keefe Z
        • Lee JF
        • Berbert A
        • et al.
        Hemodynamic responses to small muscle mass exercise in heart failure patients with reduced ejection fraction.
        American journal of physiology Heart and circulatory physiology. 2014; 307: H1512-H1520
        • Gitt AK.
        Exercise Anaerobic Threshold and Ventilatory Efficiency Identify Heart Failure Patients for High Risk of Early Death.
        Circulation. 2002; 106: 3079-3084
        • Mancini D
        • Eisen H
        • Kussmaul W
        • et al.
        Value of Peak Exercise Oxygen Consumption for Optimal Timing of Cardiac Transplantation in Ambulatory Patients With Heart Failure.
        Circulation. 1991; 83: 778-786
        • Voelkel NF
        • Quaife RA
        • Leinwand LA
        • et al.
        Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure.
        Circulation. 2006; 114: 1883-1891
        • Konstam MA
        • Kiernan MS
        • Bernstein D
        • et al.
        Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.
        Circulation. 2018; 137: e578-e622
        • Kochav SM
        • Flores RJ
        • Truby LK
        • et al.
        Prognostic Impact of Pulmonary Artery Pulsatility Index (PAPi) in Patients With Advanced Heart Failure: Insights From the ESCAPE Trial.
        J Card Fail. 2018; 24: 453-459
        • Dhakal BP
        • Malhotra R
        • Murphy RM
        • et al.
        Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction.
        Circ Heart Fail. 2015; 8: 286-294
        • Cornwell WK
        • Tran T
        • Cerbin L
        • et al.
        New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis.
        J Physiol. 2020; 598: 2575-2587
        • McCabe C
        • White PA
        • Hoole SP
        • et al.
        Right ventricular dysfunction in chronic thromboembolic obstruction of the pulmonary artery: a pressure-volume study using the conductance catheter.
        J Appl Physiol. 2014; 116 (1985): 355-363
        • Keteyian SJ
        • Patel M
        • Kraus WE
        • et al.
        Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure.
        J Am Coll Cardiol. 2016; 67: 780-789
        • Malhotra R
        • Bakken K
        • D'Elia E
        • et al.
        Cardiopulmonary Exercise Testing in Heart Failure.
        JACC Heart failure. 2016; 4: 607-616
        • Ma TS
        • Paniagua D
        • Denktas AE
        • et al.
        Usefulness of the Sum of Pulmonary Capillary Wedge Pressure and Right Atrial Pressure as a Congestion Index that Prognosticates Heart Failure Survival (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial).
        Am J Cardiol. 2016; 118: 854-859
        • Drazner MH
        • Hamilton MA
        • Fonarow G
        • et al.
        Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure.
        The Journal of heart and lung transplantation. 1999; 18: 1126-1132
        • Sailer C
        • Edelmann H
        • Buchanan C
        • et al.
        Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.
        Circulation Heart failure. 2021; 14e007448
        • Tran T
        • Muralidhar A
        • Hunter K
        • et al.
        Right ventricular function and cardiopulmonary performance among patients with heart failure supported by durable mechanical circulatory support devices.
        Journal of Heart and Lung Transplantation. 2021; 40: 128-137
        • Balady GJ
        • Arena R
        • Sietsema K
        • et al.
        Clinician's guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association.
        Circulation. 2010; 122: 191-225
        • Aalders M
        • Kok W
        Comparison of Hemodynamic Factors Predicting Prognosis in Heart Failure: A Systematic Review.
        J Clin Med. 2019; 8
        • Yancy CW
        • Jessup M
        • Bozkurt B
        • et al.
        2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        Circulation. 2013; 128: e240-e327
        • Arena R
        • Myers J
        • Aslam SS
        • et al.
        Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison.
        American heart journal. 2004; 147: 354-360
        • Maskin CS
        • Forman R
        • Sonnenblick EH
        • et al.
        Failure of Dobutamine to Increase Exercise Capacity Despite Hemodynamic Improvement in Severe Chronic Heart Failure.
        Congestive heart failure. 1983; 51
        • Wilson JR
        • Rayos GH
        • Yeoh TK
        • et al.
        Dissociation Between Peak Exercise Oxygen Consumption and Hemodynamic Dysfunction in Potential Heart Transplant Candidates.
        Journal of the American College of Cardiology. 1995; 26: 429-435
        • Mancini DM
        • Schwartz M
        • Ferraro N
        • et al.
        Effect of Dobutamine on Skeletal Muscle Metabolism in Patients with Congestive Heart Failure.
        American Journal of Cardiology. 1990; 65: 1121-1126
        • Zile MR
        • Kjellstrom B
        • Bennett T
        • et al.
        Effects of exercise on left ventricular systolic and diastolic properties in patients with heart failure and a preserved ejection fraction versus heart failure and a reduced ejection fraction.
        Circulation Heart failure. 2013; 6: 508-516
        • Wright SP
        • Granton JT
        • Esfandiari S
        • et al.
        The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults.
        J Physiol. 2016; 594: 3307-3315
        • Iglesias-Garriz I
        • Olalla-Gómez C
        • Garrote C
        • et al.
        Contribution of right ventricular dysfunction to heart failure mortality: a meta-analysis.
        Rev Cardiovasc Med. 2012; 13: e62-e69
        • Surkova E
        • Kovacs A
        • Tokodi M
        • et al.
        Contraction Patterns of the Right Ventricle Associated with Different Degrees of Left Ventricular Systolic Dysfunction.
        Circ Cardiovasc Imaging. 2021; 14e012774
        • Saouti N
        • Westerhof N
        • Postmus PE
        • et al.
        The arterial load in pulmonary hypertension.
        Eur Respir Rev. 2010; 19: 197-203
        • Dupont M
        • Mullens W
        • Skouri HN
        • et al.
        Prognostic role of pulmonary arterial capacitance in advanced heart failure.
        Circ Heart Fail. 2012; 5: 778-785
        • Dell'Italia LJ.
        Anatomy and physiology of the right ventricle.
        Cardiology clinics. 2012; 30: 167-187
        • Hsu S
        • Houston BA
        • Tampakakis E
        • et al.
        Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension.
        Circulation. 2016; 133: 2413-2422
        • Tedford RJ
        • Mudd JO
        • Girgis RE
        • et al.
        Right ventricular dysfunction in systemic sclerosis-associated pulmonary arterial hypertension.
        Circulation Heart failure. 2013; 6: 953-963
        • Edward J
        • Banchs J
        • Parker H
        • et al.
        Right ventricular function across the spectrum of health and disease.
        Heart. 2022; (in press)
        • Tran T
        • Muralidhar A
        • Hunter K
        • et al.
        Right ventricular function and cardiopulmonary performance among patients with heart failure supported by durable mechanical circulatory support devices.
        J Heart Lung Transplant. 2021; 40: 128-137
        • Spruijt OA
        • de Man FS
        • Groepenhoff H
        • et al.
        The effects of exercise on right ventricular contractility and right ventricular-arterial coupling in pulmonary hypertension.
        Am J Respir Crit Care Med. 2015; 191: 1050-1057