Cardiac troponin I: A potential marker of exercise intolerance in patients with moderate heart failure

doi:10.1067/mhj.2002.123313

American Heart Journal

Volume 144, Issue 2, August 2002, Pages 351-358

https://doi.org/10.1067/mhj.2002.123313 Get rights and content

Abstract

Background In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. Methods Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% ± 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). Results Patients with moderate heart failure showed an increase of cTnI from 37 ± 49 pg/mL to 73 ± 59 pg/mL (P <.001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P <.05 for each). Conclusion Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated. (Am Heart J 2002;144:351-8)

Section snippets

Patients

Twenty-seven patients with moderate and, as control groups, 9 patients with mild heart failure and 10 subjects with no heart failure (4 healthy volunteers and 6 cardiac patients without heart failure) were included consecutively.

All patients included in this study fulfilled the following criteria:

For all groups:

•
Exclusion of an inflammatory process by clinical signs and laboratory data
•
Exclusion of myocardial ischemia: no angina pectoris, no electrocardiographic changes during exercise test, and

Results

The clinical parameters of the investigated patient groups are shown in Table I.Data from the symptom-limited exercise test and from the training session are given in Table II.

The cTnI values during the symptom-limited exercise test and the exercise training session are shown in Table III.For patients with moderate heart failure, the peak postexercise level of cTnI, differing significantly from baseline, almost reached the cutoff value for minor myocardial damage as reported by Heeschen et al²⁹

Discussion

Our main finding was an increase of cTnI, which indicates minor myocardial damage (≥100 pg/mL), in 19% of moderate heart failure patients after symptom-limited exercise having normal values at rest. Previous studies have shown that cardiac troponins are elevated in severe heart failure30, 31, 34, 35, 36, 37 and notably during decompensation.30, 31 A comparison of absolute values is limited, as there is no standardized cTnI measuring system. A comparison of the latest cTnI and cTnT measuring

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Usefulness of high-sensitive troponin elevation after effort stress to unveil vulnerable myocardium in patients with heart failure
2015, American Journal of Cardiology
Elevation of resting high-sensitivity troponin (hs-Tn) holds prognostic value in heart failure (HF), but its pathophysiological meaning is unclear. We aimed to investigate hs-Tn elevation after maximal exercise in patients with systolic HF and its neurohormonal and hemodynamic correlates: 30 patients diagnosed with systolic HF (left ventricular ejection fraction 32 ± 8%, mean ± SD), on guideline-directed medical therapy and not recognized inducible ischemia, underwent maximal cardiopulmonary stress test, with assay of plasma N-terminal proB-type natriuretic peptide (NT-proBNP), norepinephrine (NE), and hs-TnT (hs-TnT) at baseline, peak, and 1 and 4 hours after exercise. Cardiac output (CO) was measured during effort, with a rebreathing technique. The natural logarithm of the ratio between percentage (%) increase in CO and NT-proBNP (ln[CO%/NT-proBNP% increase]) was evaluated, as a noninvasive estimate of Frank–Starling adaptation to effort, with NT-proBNP variation considered as a surrogate of end-diastolic left ventricular pressure variation. Hs-TnT increased during exercise with a 4-hour peak (p = 0.001); 10 patients had hs-TnT increase >20%. Patients with Hs-TnT increase >20% were more symptomatic at rest (p = 0.039) and showed greater NE at peak exercise (p = 0.003) and less ln[CO%/NT-proBNP% increase] (p = 0.034). A lower ln[CO%/NT-proBNP% increase] correlated with greater NE at peak exercise (r = −0.430, p = 0.018). In conclusion, acute troponin elevation after maximal exercise was detected in 1/3 of this series. The association of troponin release with NE, CO, and NT-proBNP changes after effort suggests a pathophysiological link among transient hemodynamic overload, adrenergic activation, and myocardial cell damage, likely identifying a clinical subset at greater risk for HF progression.
Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina
2015, JACC: Heart Failure
Citation Excerpt :
Troponin I levels were abnormal in 2 patients after exercise; in each case, the levels were just above the upper laboratory reference limit and occurred in the absence of other clinical signs or symptoms of cardiac ischemia. The background rate of detectable troponin after exercise testing in this patient population is not well established, but was approximately 10% in 2 small studies (13,14). Given the number of patients studied, our findings do not rule out the possibility that increases in troponin I might occur in some heart failure patients with coronary disease during exercise while receiving omecamtiv mecarbil treatment, but they do indicate that the occurrence of this event is likely to be low.
The goal of this study was to assess the safety and tolerability of omecamtiv mecarbil treatment during symptom-limited exercise in patients with ischemic cardiomyopathy and angina. These patients may have increased vulnerability to prolongation of the systolic ejection time.
Omecamtiv mecarbil is a selective cardiac myosin activator that augments cardiac contractility in patients with systolic heart failure through a dose-dependent increase in systolic ejection time.
In this double-blind, placebo-controlled study, patients with chronic heart failure were randomized 2:1 to receive omecamtiv mecarbil or placebo in 2 sequential cohorts of escalating doses designed to achieve plasma concentrations previously shown to increase systolic function. Patients underwent 2 symptom-limited exercise treadmill tests (ETTs) at baseline (ETT1 and ETT2) and again before the end of a 20-h infusion of omecamtiv mecarbil (ETT3).
The primary pre-defined safety endpoint (i.e., the proportion of patients who stopped ETT3 because of angina at a stage earlier than baseline) was observed in 1 patient receiving placebo and none receiving omecamtiv mecarbil. No dose-dependent differences emerged in the proportion of patients stopping ETT3 for any reason or in the pattern of adverse events.
Doses of omecamtiv mecarbil producing plasma concentrations previously shown to increase systolic function were well tolerated during exercise in these study patients with ischemic cardiomyopathy and angina. There was no indication that treatment increased the likelihood of myocardial ischemia in this high-risk population. (Pharmacokinetics [PK] and Tolerability of Intravenous [IV] and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina; NCT00682565)
Troponin and others markers of myocardial ischemia injury, which relevance in internal medicine?
2006, Revue de Medecine Interne
Propos. – La troponine occupe désormais une place essentielle dans le diagnostic d'infarctus du myocarde. Avec pour objectif d'améliorer la pratique quotidienne du praticien face à une suspicion d'évolutivité coronarienne, la présente mise au point se propose de préciser l'interprétation des dosages de troponine en fonction du contexte clinique et des pathologies associées.
Actualités et points forts. – Dans un premier temps, la place de la troponine par rapport aux autres marqueurs d'ischémie coronarienne sera précisée. Ensuite, les données de la littérature disponibles sur la troponine dans les pathologies cardiovasculaires mais aussi dans les pathologies extracardiaques seront analysées. Enfin, les difficultés techniques du dosage seront abordées.
Perspectives et projets. – La possibilité de disposer d'un marqueur aussi sensible et spécifique que la troponine est incontestablement un progrès pour la prise en charge des patients atteints de syndrome coronaire aigu. Il n'en reste pas moins un outil au service de la prise en charge d'un patient dans son ensemble. Il est donc essentiel de connaître les circonstances susceptibles de modifier les taux sous peine de mauvaise interprétation du dosage, pouvant conduire à des erreurs à la fois diagnostiques mais aussi thérapeutiques.
Purpose. – Troponin is now the gold standard for the diagnosis of myocardial infarction. Aiming at improving the management of a patient suspect of an acute coronary syndrome, this article will point the interpretation of troponin dosages according to the clinical presentation and concomitant diseases.
Actualities. – First, the interest of troponin dosage as compared with other markers of myocardial ischemia will be underlined. Then, the literature available about troponin in cardiovascular diseases but also in extracardiac diseases will be analysed. Finally, the difficulties of assay will be discussed.
Perspectives. – The availability of a sensitive and specific marker such as troponin is definitively a progress in the management of patients with an acute coronary syndromes. But it remains a biological contribution to the global management of the patient. It is important to know the causes susceptible to increase the levels of troponin to avoid a wrong interpretation of the dosage, leading to diagnostic but also therapeutic mistakes.
Cardiac troponin I and T: Specific biomarkers of cardiomyocyte
2004, Revue de Medecine Interne
Propos. – Le dosage de la troponine cardiaque, qu’il s’agisse de la I ou de la T, remplace aujourd’hui celui de la créatine kinase MB (CK-MB) pour le diagnostic d’une nécrose du cardiomyocyte. La cardiospécificité de ces nouveaux marqueurs doit conduire à un changement d’habitude dans l’interprétation des résultats.
Actualités et points forts. – Lors d’une nécrose du cardiomyocyte, des protéines intracellulaires sont libérées dans la circulation sanguine. Ce concept simple recouvre en fait une complexité biologique pour les troponines qui sont libérées majoritairement sous forme de complexes ; cette complexité contribue à l’existence de valeurs de seuil de positivité très différentes d’une trousse de dosage à une autre, au moins pour la troponine I cardiaque. La cardiospécifité de ces marqueurs et la sensibilité analytique des trousses de dosage ont contribué à la proposition d’une nouvelle définition de l’infarctus du myocarde. Dans les syndromes coronariens aigus, le diagnostic repose essentiellement sur la clinique, le dosage des troponines n’apportant qu’une aide au diagnostic et contribuant à leur classification. Enfin, toute pathologie ayant un retentissement cardiaque peut entraîner une augmentation de ces marqueurs.
Perspectives. – La standardisation de ces dosages devrait améliorer le suivi des patients et la comparaison des résultats dans les études de cohorte.
Purpose. – Cardiac troponin I and troponin T have replaced creatine kinase MB (CK-MB) for the diagnosis of cardiomyocyte necrosis. Cardiac specificity of these new markers leads to a change in our practice.
Current knowledge and key points. – Following necrosis, intracellular proteins are released into blood. This easy concept overlaps a biological complexity since troponins are released as complexes leading to various cut-off values depending on the assay used, as least for cardiac troponin I. The increase in both specificity and analytical sensitivity of these markers reached to propose a new definition of myocardial infarction. The diagnosis of acute coronary syndrome is a clinical based diagnosis, the use of troponin contributing to their classification. Finally, pathological processes leading to cardiac injury may induce an increase in the cardiac troponin level.
Future prospects and projects. – Troponin standardization is a challenge for the near future leading to better follow-up of patients and comparison between cohorts.
Impact of an exercise-induced increase in cardiac troponin I in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy
2002, American Journal of Cardiology
Significance of serum insulin combined with cardiac markers in evaluating sepsis associated encephalopathy
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^☆: Reprint requests: Olaf Schulz, MD, Cooperative Interventional Cardiology Berlin-Spandau, Neuendorfer Str 70, 13585 Berlin, Germany.

^☆☆: E-mail: [email protected]

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Clinical Investigations: Congestive Heart FailureCardiac troponin I: A potential marker of exercise intolerance in patients with moderate heart failure☆,☆☆

Abstract

Section snippets

Patients

Results

Discussion

J Cardiac Failure

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am Heart J

Am Heart J

Am Heart J

Am J Cardiol

Am Heart J

Am Heart J

Exercise training in heart failure improves quality of life and exercise capacity

Eur Heart J

Safety and effects of physical training in chronic heart failure: results of the chronic heart failure and graded exercise study (CHANGE)

Eur Heart J

Low intensity exercise training in patients with chronic heart failure

J Am Coll Cardiol

Exercise training in patients with severe left ventricular dysfunction: hemodynamic and metabolic effects

Circulation

Skeletal muscle response to exercise training in congestive heart failure

J Clin Invest

Training partially reverses skeletal muscle metabolic abnormalities during exercise in heart failure

J Appl Physiol

The effect of physical training on hormonal status and exertional hormonal response in patients with chronic congestive heart failure

Eur Heart J

Clinical Investigations: Congestive Heart Failure
Cardiac troponin I: A potential marker of exercise intolerance in patients with moderate heart failure☆,☆☆