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A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure
Published on: April 30, 2020
Association Between Circulating Troponin Concentrations, Left Ventricular Systolic and Diastolic Functions, and
Peder L Myhre1,2, Brian Claggett1, Christie M Ballantyne3
1Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Insights
High-sensitivity cardiac troponin T (hs-cTnT) is linked to worse diastolic function, not systolic, and may predict heart failure risk. Elevated hs-cTnT and diastolic dysfunction are additive risk factors for heart failure.
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure Research
Background:
- Cardiac troponin is linked to heart failure and left ventricular (LV) mass.
- The association between cardiac troponin and LV systolic/diastolic function is not well-defined.
Purpose of the Study:
- To determine the association between high-sensitivity cardiac troponin T (hs-cTnT) and LV systolic and diastolic functions in the general population.
- To assess how hs-cTnT-associated cardiac function explains the link between hs-cTnT levels and incident heart failure (HF), including HF with preserved ejection fraction (HFpEF).
Main Methods:
- Analysis of the Atherosclerosis Risk in Communities (ARIC) Study cohort (n=4111) without pre-existing cardiovascular disease.
- Cross-sectional assessment of hs-cTnT levels against echocardiographic measures and longitudinal assessment against incident heart failure.
- Statistical analysis performed from August 2017 to July 2018.
Main Results:
- Higher hs-cTnT levels correlated with increased LV mass index and worse diastolic function (lower e', higher E/e', greater left atrial volume index), independent of LV mass.
- hs-cTnT levels were not associated with LV systolic function.
- Diastolic dysfunction partially mediated the association between hs-cTnT and incident HFpEF (41% attenuation) and HF with LVEF <50 (17% attenuation).
- Elevated hs-cTnT and diastolic dysfunction were additive risk factors for heart failure.
Conclusions:
- Higher hs-cTnT concentrations are associated with impaired diastolic function, not systolic function, irrespective of LV mass.
- These findings suggest hs-cTnT may be an early indicator of subclinical diastolic dysfunction, potentially predisposing individuals to heart failure.
- Elevated hs-cTnT and diastolic dysfunction represent additive risks for developing heart failure.
Importance:
Cardiac troponin is associated with incident heart failure and greater left ventricular (LV) mass. Its association with LV systolic and diastolic functions is unclear.
Objectives:
To define the association of high-sensitivity cardiac troponin T (hs-cTnT) with LV systolic and diastolic functions in the general population, and to evaluate the extent to which that association accounts for the correlation between hs-cTnT concentration and incident heart failure overall, heart failure with preserved LV ejection fraction (LVEF; HFpEF), and heart failure with LVEF less than 50%.
Design, Setting, And Participants:
This analysis of the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing epidemiologic cohort study in US communities, included participants without cardiovascular disease (n = 4111). Available hs-cTnT measurements for participants who attended ARIC Study visits 2 (1990 to 1992), 4 (1996 to 1998), and 5 (2011 to 2013) were assessed cross-sectionally against echocardiographic measurements taken at visit 5 and against incident health failure after visit 5. Changes in hs-cTnT concentrations from visits 2 and 4 were also examined. Data analyses were performed from August 2017 to July 2018.
Main Outcomes And Measures:
Cardiac structure and function by echocardiography at visit 5, and incident heart failure during a median 4½ years follow-up after visit 5.
Results:
Of the 6538 eligible participants, 4111 (62.9%) without cardiovascular disease were included. Among these participants, 2586 (62.9%) were female, and the mean (SD) age was 75 (5) years. Median (interquartile range) hs-cTnT concentration at visit 5 was 9 (7-14) ng/L and was detectable in 3946 participants (96.0%). After adjustment for demographic and clinical covariates, higher hs-cTnT levels were associated with greater LV mass index (adjusted mean [SE] for group 1: 33.8 [0.5] vs group 5: 40.1 [0.4]; P for trend < .001) and with worse diastolic function, including lower tissue Doppler imaging e' (6.00 [0.07] vs 5.54 [0.06]; P for trend < .001), higher E/e' ratio (11.4 [0.2] vs 12.9 [0.1]; P for trend < .001), and greater left atrial volume index (23.4 [0.4] vs 26.4 [0.3]; P for trend < .001), independent of LV mass index; hs-cTnT level was not associated with measures of LV systolic function. Accounting for diastolic function attenuated the association of hs-cTnT concentration with incident HFpEF by 41% and the association with combined heart failure with midrange and reduced ejection fraction combined (LVEF <50) by 17%. Elevated hs-cTnT concentration and diastolic dysfunction were additive risk factors for incident heart failure. For any value of late-life hs-cTnT levels, longer duration of detectable hs-cTnT from midlife to late life was associated with greater LV mass in late life but not with worse LV systolic or diastolic function.
Conclusions And Relevance:
This study shows that higher hs-cTnT concentrations were associated with worse diastolic function, irrespective of LV mass, but not with systolic function; these findings suggest that high levels of hs-cTnT may serve as an early marker of subclinical alterations in diastolic function that may lead to a predisposition to heart failure.
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