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Myocardial Injury and Cardiac Reserve in HFpEF
Study Questions:
Does myocardial injury contribute to the hemodynamic derangements and cardiac reserve limitations that are present in heart failure and preserved ejection fraction (HFpEF)?
Methods:
The EXEC (Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease) study authors measured markers of cardiomyocyte injury, central hemodynamics, ventricular function, and determinants of cardiac oxygen supply–demand balance in HFpEF patients (n = 38) and control subjects without heart failure (n = 20). The presence or absence of HFpEF was determined using invasive cardiopulmonary exercise testing in all participants. HFpEF was defined by typical clinical symptoms (dyspnea, fatigue), normal left ventricular ejection fraction (LVEF) (≥50%), and elevated left heart filling pressures (pulmonary capillary wedge pressure) at rest (>15 mm Hg) and/or with exercise (≥25 mm Hg). The study cohort underwent cardiac catheterization, echocardiography, and expired gas analysis at rest and during exercise, and central venous blood was sampled to measure plasma high-sensitivity troponin T levels (as an index of cardiomyocyte injury).
Results:
The study authors found that when compared with control subjects, troponins were more than twofold higher in HFpEF patients at rest and during exercise (p < 0.0001). Troponin levels were directly correlated with LV filling pressures (r = 0.52; p < 0.0001) and diastolic dysfunction (r = -0.43; p = 0.002); as well as N-terminal pro–B-type natriuretic peptide (r = 0.58; p < 0.0001) and growth differentiation factor-15 (r = 0.67; p < 0.0001). 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.
Conclusions:
The study co-authors concluded that limitations 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 troponin levels.
Perspective:
This is an important study because it suggests that elevations of troponin (i.e., myocardial injury) can occur in the absence of ischemia. These findings are not dissimilar to a study published in this journal in a swine model (J Am Coll Cardiol 2018;71:2906–16). These findings suggest that strategies to reduce microvascular myocardial ischemia may be beneficial in HFpEF patients.
Keywords: Biomarkers, Cardiac Catheterization, Diastole, Dyspnea, Echocardiography, Exercise Test, Growth Differentiation Factor 15, Heart Failure, Hemodynamics, Myocardial Ischemia, Myocytes, Cardiac, Natriuretic Peptide, Brain, Peptide Fragments, Stroke Volume, Systole, Troponin I, Troponin T, Vascular Diseases, Ventricular Function
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