Left Ventricular Abnormal Response During Dynamic Exercise in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction at Rest

doi:10.1016/j.cardfail.2008.02.012

Journal of Cardiac Failure

Volume 14, Issue 6, August 2008, Pages 475-480

https://doi.org/10.1016/j.cardfail.2008.02.012 Get rights and content

Abstract

Background

The mechanisms that contribute to limit functional capacity are incompletely understood in patients with preserved resting ejection fraction (HFpREF). We assessed left ventricular (LV) systolic response to dynamic exercise in patients with HFpREF and in patients with similar comorbidities to HFpREF patients but without history or evidence of heart failure.

Methods and Results

Twenty-five HFpREF patients in steady-state clinical condition without significant coronary artery disease and 25 hypertensive controls underwent exercise echocardiography. At rest, systolic pulmonary artery pressure, left atrial area, E/A and E/e′ ratios were greater in patients with HFpREF than in control patients, whereas peak systolic mitral annular velocity was lower in HFpREF patients. The exercise-induced changes in LVEF, forward stroke volume, and cardiac output were significantly lower in HFpREF compared with control patients (–4 ± 8 vs. +6 ± 6 %, P = .001; –4 ± 9 vs. +10 ± 10 mL, P < .0001, and 1.6 ± 1.2 vs. 3.5 ± 1.8 L/min, P < .0001, respectively). Exercise-induced changes in effective arterial elastance significantly differed in HFpREF and control patients (0.5 ± 0.6 vs. –0.2 ± 0.5 mm Hg/mL, P < .0001). In addition, 7 of the 25 HFpREF patients developed functional mitral regurgitation during exercise and none in controls.

Conclusions

When compared with patients with similar comorbidities but without history or evidence of heart failure, patients with HFpREF experience greater arterial stiffening and thereby a deterioration of global LV systolic performance during dynamic exercise.

Section snippets

Patients with HFpREF

Between October 2005 and June 2006, we screened 125 patients who were hospitalized at our institution with clinical (pulmonary crackles/peripheral edema) and radiographic (pulmonary vascular redistribution/interstitial edema/pleural effusion) evidences of heart failure and a preserved LVEF on admission (≥50%). Patients presenting with arrhythmias (n = 29), bradycardia related to atrioventricular or sinoatrial blocks (n = 5), primary valvular disease (n = 22), acute coronary syndromes (n = 18),

Resting Parameters

The clinical, laboratory, and therapeutic parameters of the 25 patients with HFpREF and of the 25 patients who served as controls are summarized in Table 1. Except for the use of loop diuretics, none of the baseline parameters were statistically different between HFpREF and control patients. Of note, estimated glomerular filtration rate tended to be lower in HFpREF patients than in controls (P = .09), and BNP levels were significantly higher in HFpREF patients than in controls (P = .005). Among

Discussion

The present data indicate that, although apparently normal at rest, global LV systolic performance may deteriorate during dynamic exercise in patients with HFpREF. Heart rate, blood pressure, and LV end-diastolic volume increased similarly during exercise in HFpREF and control patients. In contrast, LV end-systolic volume increased during exercise in HFpREF patients, whereas it did not increase in control patients. As a result, LV stroke volume and cardiac output were significantly lower at

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Epidemiology, Diagnosis, Pathophysiology, and Initial Approach to Heart Failure with Preserved Ejection Fraction
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Citation Excerpt :
This not only reduces forward stroke volume, but also affects early diastolic filling.9,36 An inability to reduce vascular resistance with exercise is one reason that patients with HFpEF are unable to increase stroke volume with exercise.52,53 Reddy and colleagues52 evaluated 98 patients with HFpEF and 22 patients with hypertension without HFpEF using cardiopulmonary exercise testing, right heart catheterization, and invasive blood pressure (BP) monitoring.
Arterial stiffness and pulsatile hemodynamics in heart failure
2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease
Arterial load exerts a profound impact on left ventricular structure and function. Assessments of pulsatile arterial hemodynamics have provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, and failure. Moreover, pulsatile arterial load may interact with the distal microvasculature, promoting microvascular dysfunction and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance in heart failure (HF). Arterial pulsatile hemodynamic mechanisms also contribute to the pathogenesis of comorbidities present among patients with HF, such as renal failure and cognitive dysfunction. Specific abnormalities in pulsatile load may be susceptible to novel pharmacologic interventions. Given the heterogeneity of HF, our therapeutic approach to HF can be enhanced by detailed phenotyping of arterial hemodynamics, which can contribute to the segmentation of the HF population into relevant pathophysiologic categories, or to identifying individuals exhibiting prominent physiologic abnormalities that can be targeted by pharmacologic interventions. This is particularly relevant for heart failure with preserved ejection fraction (HFpEF), which is now the most common form of HF, and for which limited therapeutic options exist.
Peripheral Oxygen Extraction and Exercise Limitation in Asymptomatic Patients with Diabetes Mellitus
2021, American Journal of Cardiology
Citation Excerpt :
Dhakal et al. performed CPX with invasive hemodynamic monitoring in 104 symptomatic patients with HF among whom 48 patients presented HFpEF and demonstrated that peripheral oxygen extraction (arterio-venous oxygen difference) was a major determinant of exercise capacity in HFpEF.4 Patients with HFpEF presented reduced stroke volume or cardiac output at peak compared to controls in their study, which was similar to other studies.29,30 In contrast, asymptomatic participants in our study presented maintained stroke volume as well as cardiac output at peak, even though systolic function assessed by LVLS was impaired at rest.
Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO₂) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO₂). Peripheral extraction was calculated as the ratio of VO₂ to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e’, and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO₂(<80%) and 18 (18%) presented abnormal VE/VCO₂slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e’ (beta = -0.24, p = 0.004) was associated with lower peak VO₂ along with age, sex and body mass index (R² = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e’, relative wall thickness and peak VO₂ in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO₂in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM.
Sex-Related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart Failure With Preserved Ejection Fraction
2021, Chest
Right ventricular (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Although female subjects are more likely to have HFpEF, male subjects have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary arterial (RV-PA) coupling between sex and its impact on peak exercise capacity (VO₂) in HFpEF is not known.
The goal of this study was to investigate the differential effects of sex on RV-PA coupling during maximum incremental exercise in patients with HFpEF.
This study examined rest and exercise invasive pulmonary hemodynamics in 22 male patients with HFpEF and 27 female patients with HFpEF. To further investigate the discrepancy in RV-PA response between sex, 26 age-matched control subjects (11 male subjects and 15 female subjects) were included. Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance. RV-PA coupling was determined as the ratio of end-systolic elastance/PA elastance.
Both HFpEF groups experienced decreased peak VO₂ (% predicted). However, male patients with HFpEF experienced a greater decrement in peak VO₂ compared with female patients (58 ± 16% vs 70 ± 15%; P < .05). Male patients with HFpEF had a more pronounced increase in RV afterload, Ea (1.8 ± 0.6 mm Hg/mL/m² vs 1.3 ± 0.4 mm Hg/mL/m²; P < .05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs 1.2 ± 0.4; P < .05) and subsequent reduced stroke volume index augmentation. In contrast, female patients with HFpEF were able to augment RV contractility in the face of increasing afterload, preserving RV-PA coupling during exercise.
Male patients with HFpEF were more compromised regarding dynamic RV-PA uncoupling and reduced peak VO₂ compared with female patients. This finding was driven by both RV contractile impairment and afterload mismatch. In contrast, female patients with HFpEF had preserved RV-PA coupling during exercise and better peak exercise VO₂ compared with male patients with HFpEF.
Heart failure with preserved ejection fraction: A systemic disease linked to multiple comorbidities, targeting new therapeutic options
2018, Archives of Cardiovascular Diseases
Heart failure is a pathology associated with severe morbidity and mortality. In this large field, heart failure with preserved ejection fraction (HFpEF) appears to be an increasing global health problem; it should be considered as a progressive syndrome, characterized by complex mechanisms of systemic and cardiac adaptation that vary over time, particularly with ageing. Multiple biological phenotypes contribute to the heterogeneous clinical syndrome. HFpEF emerges as a model with proinflammatory cardiovascular and non-cardiovascular coexisting comorbidities, leading to systemic inflammation and subsequent fibrosis and to diverse clinical HFpEF phenotypes. All of these aspects are often present in the elderly population, bordering on the emergence of a true geriatric syndrome. The therapeutic approach cannot be uniform, and must involve management of the different comorbidities according to a phenotype treatment strategy, respecting the pharmacological approaches to the biological pathways involved in the proinflammatory comorbidity-related status. Future studies should consider these multiple distinct HFpEF phenotypes in the development of large morbimortality trials adapted to comorbidities or specific risk factors.
L’insuffisance cardiaque est une pathologie associée avec une mortalité et une morbidité sévère. Dans ce champ très large, l’insuffisance cardiaque à fraction d’éjection préservée (ICFEp) apparaît comme un problème de santé global en aggravation. Elle doit être considérée comme un syndrome progressif caractérisé par des mécanismes complexes d’adaptation systémique et cardiaque qui varie sur le temps, particulièrement chez le sujet âgé. De multiples phénotypes biologiques contribuent à ce syndrome clinique hétérogène. L’ICFEp émerge comme un modèle avec des comorbidités cardiovasculaires et non cardiovasculaires coexistantes pro-inflammatoires conduisant à une inflammation systémique et une fibrose consécutive et à divers phénotypes cliniques d’ICFEp. Tous ces aspects sont souvent présents chez le sujet âgé confinant à l’émergence d’un véritable syndrome gériatrique. L’approche thérapeutique ne peut pas en être uniforme et doit conduire à prendre en charge les différentes comorbidités selon une stratégie de traitement par phénotype, en respectant une approche pharmacologique des différentes voies biologiques impliquées dans l’état pro-inflammatoire lié aux comorbidités. Les études futures devront considérer ces phénotypes multiples distincts d’ICFEp pour développer des grands essais de morbi-mortalité adaptés aux comorbidités ou aux facteurs de risque spécifiques.
Heart Failure With Preserved Ejection Fraction—A Systematic Review and Analysis of Perioperative Outcomes
2018, Journal of Cardiothoracic and Vascular Anesthesia

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: P.V.E. and S.M. contributed equally to the preparation of the manuscript.

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Clinical InvestigationLeft Ventricular Abnormal Response During Dynamic Exercise in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction at Rest

Abstract

Background

Methods and Results

Conclusions

Section snippets

Patients with HFpREF

Resting Parameters

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

J Card Fail

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Soc Echocardiogr

Heart failure with a normal ejection fraction: is it really a disorder of diastolic function?

Circulation

Diastolic heart failure—abnormalities in active relaxation and passive stiffness of the left ventricle

N Engl J Med

Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations

Circulation

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction

Circulation

Clinical Investigation
Left Ventricular Abnormal Response During Dynamic Exercise in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction at Rest