High-Sensitivity Troponin T in Stable Heart Failure
Troponin levels are used in the diagnosis of acute coronary syndromes (ACS), however, levels may be elevated in many other conditions. A significant proportion of patients with stable heart failure (HF) have detectable levels of troponin using standard assays, however, the incidence of detectable levels of high-sensitivity troponin T (hsTnT) in HF patients is not extensively studied.
As part of a trial assessing vascular function in stable HF patients, 32 subjects had hsTnT levels measured at baseline using a multi-channel analyser (Roche E Module). At baseline, 27 (84.4%) patients had detectable levels of hsTnT (median 13.8 ng/L, range 9.2–21.4): 12 (75%) patients in the non-ischaemic group and 15 (94%) in the ischaemic group. A total of 14 (43.8%) patients had levels above the 99th percentile of the normal range.
The majority of patients with stable HF will have detectable levels of troponin T using new high-sensitivity assays. A significant proportion of these will be above the cut-off point used for diagnosis of ACS. If these patients present to hospital, modest elevations in hsTnT do not necessarily indicate recent ACS, and serial measurements should be undertaken if clinically indicated.
Troponins are proteins found within cardiac and skeletal muscle fibres with the physiological role of muscle fibre contraction by allowing cross bridging between actin and myosin filaments. In certain situations these intracellular molecules can be detected in the plasma, indicating loss of integrity of the cell membrane. In most cases this is due to cardiac ischaemia or infarction, and troponins have a well-established role in the diagnosis and risk stratification of acute coronary syndromes (ACS). However, many other cardiac and non-cardiac conditions may result in detectable levels of cardiac troponins in plasma (Box 1).
Mechanistically, these low level elevations may signify leakage of the cytosolic pool of troponin during reversible injury or cell stretch. Ischaemia may be caused by a mismatch between oxygen supply and demand at a cellular level. Wall stress may be increased by chamber dilation and elevated filling pressures resulting in increased oxygen demands, while oxygen supply is reduced by factors such as anaemia, hypotension and reduced gas transfer. Progressive apoptotic and necrotic cell death have also been implicated in heart failure (HF) due to influences such as inflammatory cytokines and oxidative stress, which have a direct cytotoxic effect, although some evidence suggests that wall stress can lead directly to myocardial cell death independently of ischaemia. Another theory suggests that intracellular proteolysis may allow release of troponin fragments, which may have affinity for immunoassays.
Several studies have reported elevated levels of cardiac troponins in patients with HF in the absence of ACS, and, as in ACS, degree of troponin elevation correlates with worse prognosis. A recent review of troponin elevations in HF found an overall hazard ratio of 2.85 (95% confidence interval [CI] 2.02, 4.03) for mortality in patients with elevated troponin.Table 1 summarises significant studies of troponin levels in HF patients.
More recently, the need for a biomarker with adequate precision and a low coefficient of variation at the upper limit of normal in the reference population, has prompted development of a new generation of troponin assay. A fourth-generation high-sensitivity troponin T (hsTnT) assay developed by Roche can now detect troponin T levels down to 3 ng/L with a 99 percentile value of 14 ng/L in the normal population. Tentzeris et al. found hsTnT to be elevated in 58% of patients with chronic stable heart failure, and in a Japanese study of 85 patients with dilated cardiomyopathy, hsTnT was elevated in 54% of patients (compared with only 5% with elevation of conventional troponin T), and again, was an independent predictor of worse prognosis. Elevated troponin levels in HF patients tend to be more common when measured using high-sensitivity assays compared with earlier generation assays, although there is wide variation between studies (11–54% for low-sensitivity assays and 43–92% for high-sensitivity assays). Patients with HF tend to have multiple hospital admissions and may have troponin levels measured on admission. The finding of a raised troponin may suggest possible ACS and lead to unnecessary and potentially harmful treatment. The frequency and degree of troponin elevation in stable HF patients without ACS, particularly using new high-sensitivity assays is, therefore, of interest.
Abstract and Introduction
Abstract
Troponin levels are used in the diagnosis of acute coronary syndromes (ACS), however, levels may be elevated in many other conditions. A significant proportion of patients with stable heart failure (HF) have detectable levels of troponin using standard assays, however, the incidence of detectable levels of high-sensitivity troponin T (hsTnT) in HF patients is not extensively studied.
As part of a trial assessing vascular function in stable HF patients, 32 subjects had hsTnT levels measured at baseline using a multi-channel analyser (Roche E Module). At baseline, 27 (84.4%) patients had detectable levels of hsTnT (median 13.8 ng/L, range 9.2–21.4): 12 (75%) patients in the non-ischaemic group and 15 (94%) in the ischaemic group. A total of 14 (43.8%) patients had levels above the 99th percentile of the normal range.
The majority of patients with stable HF will have detectable levels of troponin T using new high-sensitivity assays. A significant proportion of these will be above the cut-off point used for diagnosis of ACS. If these patients present to hospital, modest elevations in hsTnT do not necessarily indicate recent ACS, and serial measurements should be undertaken if clinically indicated.
Introduction
Troponins are proteins found within cardiac and skeletal muscle fibres with the physiological role of muscle fibre contraction by allowing cross bridging between actin and myosin filaments. In certain situations these intracellular molecules can be detected in the plasma, indicating loss of integrity of the cell membrane. In most cases this is due to cardiac ischaemia or infarction, and troponins have a well-established role in the diagnosis and risk stratification of acute coronary syndromes (ACS). However, many other cardiac and non-cardiac conditions may result in detectable levels of cardiac troponins in plasma (Box 1).
Mechanistically, these low level elevations may signify leakage of the cytosolic pool of troponin during reversible injury or cell stretch. Ischaemia may be caused by a mismatch between oxygen supply and demand at a cellular level. Wall stress may be increased by chamber dilation and elevated filling pressures resulting in increased oxygen demands, while oxygen supply is reduced by factors such as anaemia, hypotension and reduced gas transfer. Progressive apoptotic and necrotic cell death have also been implicated in heart failure (HF) due to influences such as inflammatory cytokines and oxidative stress, which have a direct cytotoxic effect, although some evidence suggests that wall stress can lead directly to myocardial cell death independently of ischaemia. Another theory suggests that intracellular proteolysis may allow release of troponin fragments, which may have affinity for immunoassays.
Several studies have reported elevated levels of cardiac troponins in patients with HF in the absence of ACS, and, as in ACS, degree of troponin elevation correlates with worse prognosis. A recent review of troponin elevations in HF found an overall hazard ratio of 2.85 (95% confidence interval [CI] 2.02, 4.03) for mortality in patients with elevated troponin.Table 1 summarises significant studies of troponin levels in HF patients.
More recently, the need for a biomarker with adequate precision and a low coefficient of variation at the upper limit of normal in the reference population, has prompted development of a new generation of troponin assay. A fourth-generation high-sensitivity troponin T (hsTnT) assay developed by Roche can now detect troponin T levels down to 3 ng/L with a 99 percentile value of 14 ng/L in the normal population. Tentzeris et al. found hsTnT to be elevated in 58% of patients with chronic stable heart failure, and in a Japanese study of 85 patients with dilated cardiomyopathy, hsTnT was elevated in 54% of patients (compared with only 5% with elevation of conventional troponin T), and again, was an independent predictor of worse prognosis. Elevated troponin levels in HF patients tend to be more common when measured using high-sensitivity assays compared with earlier generation assays, although there is wide variation between studies (11–54% for low-sensitivity assays and 43–92% for high-sensitivity assays). Patients with HF tend to have multiple hospital admissions and may have troponin levels measured on admission. The finding of a raised troponin may suggest possible ACS and lead to unnecessary and potentially harmful treatment. The frequency and degree of troponin elevation in stable HF patients without ACS, particularly using new high-sensitivity assays is, therefore, of interest.
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