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Relative Impairments in Hemodynamic Exercise Reserve Parameters in Heart Failure With Preserved Ejection Fraction: A Study-Level Pooled Analysis.

ABSTRACT:

Objectives

The aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis.

Background

A cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance.

Methods

Data were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise - resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis.

Results

The pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: -2.13; 95% confidence interval [CI]: -2.68 to -1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: -1.87; 95% CI: -2.44 to -1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups.

Conclusions

The most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.

SUBMITTER: Pandey A

PROVIDER: S-EPMC8135913 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCardiac reserve is depressed in patients with heart failure and preserved ejection fraction (HFpEF). The mechanisms causing this are poorly understood.ObjectivesThe authors hypothesized that myocardial injury might contribute to the hemodynamic derangements and cardiac reserve limitations that are present in HFpEF. Markers of cardiomyocyte injury, central hemodynamics, ventricular function, and determinants of cardiac oxygen supply-demand balance were measured.MethodsSubjects with HFpEF (n = 38) and control subjects without heart failure (n = 20) underwent cardiac catheterization, echocardiography, and expired gas analysis at rest and during exercise. Central venous blood was sampled to measure plasma high-sensitivity troponin T levels as an index of cardiomyocyte injury.ResultsCompared with control subjects, troponins were more than 2-fold higher in subjects with HFpEF at rest and during exercise (p < 0.0001). Troponin levels were directly correlated with left ventricular (LV) filling pressures (r = 0.52; p < 0.0001) and diastolic dysfunction (r = -0.43; p = 0.002). Although myocardial oxygen demand was similar, myocardial oxygen supply was depressed in HFpEF, particularly during exercise (coronary perfusion pressure-time integral; 44 ± 9 mm Hg × s × min-1 × l × dl-1 vs. 30 ± 9 mm Hg × s × min-1 × l × dl-1; p < 0.0001), and reduced indices of supply were correlated with greater myocyte injury during exercise (r = -0.44; p = 0.0008). Elevation in troponin with exercise was directly correlated with an inability to augment LV diastolic (r = -0.40; p = 0.02) and systolic reserve (r = -0.57; p = 0.0003), greater increases in LV filling pressures (r = 0.55; p < 0.0001), blunted cardiac output response (r = -0.44; p = 0.002), and more severely depressed aerobic capacity in HFpEF.ConclusionsLimitations in LV functional reserve and the hemodynamic derangements that develop secondary to these limitations during exercise in HFpEF are correlated with the severity of cardiac injury, assessed by plasma levels of troponin T. Further study is warranted to determine the mechanisms causing myocyte injury in HFpEF and the potential role of ischemia, and to identify and test novel interventions targeted to these mechanisms. (EXEC [Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease]; NCT01418248).