523 Troponin I could stratify the patients with severe heart failure

Introduction: Inotrope use is associated with adverse outcomes in heart failure (HF), raising concern that it may cause or accelerate myocardial injury/damage. Whether biomarkers of myocardial necrosis, stretch, inflammation and apoptosis change in response to inotrope initiation is not known. Methods: Ten patients with severe HF and cardiac index < 2.0 L/m/M2 who were planned to receive intravenous milrinone were studied. All patients were at bed rest in cardiac intensive care unit. Blood was drawn immediately before initiation of milrinone and after 24 hours of continuous infusion. Milrinone dosing was at the discretion of the patient’s attending physician (0.375 –0.5 mcg/kg/min were used). Blood samples were immediately centrifuged, plasma aliquoted, and frozen at -70°C. Troponin I (TnI), Myoglobin, N-terminal pro-BNP (NTproBNP), interleukin 6 (IL6), Tumor Necrosis Factor α (TNF α), soluble Fas (sFas), and Fas ligand (FasL) levels were measured. TnI levels were replicated to assess precision of measurement, yielding a correlation coefficient > 0.995 and power > 90% to detect a mean difference as small as 0.02 ng/ml. Statistical comparisons were made between baseline levels and 24 hour levels using the paired t-test. P values < 0.05 were considered significant. Results: Baseline mean biomarker levels, 24 hour levels, absolute change, percent change, and associated p-values are shown in the Table . Troponin I was elevated at baseline in all patients (range 0.0205– 0.56 ng/ml). There was no significant change in TnI after 24 hours of milrinone compared to baseline. There were significant improvements in NTproBNP, IL6, TNF α, sFas, and FasL. Conclusions: In this sample of patients with severe HF and reduced cardiac output, all had elevated troponin at baseline, consistent with ongoing myocardial damage. Initiation of milrinone therapy did not result in changes indicative of accelerated myocardial injury, and was associated with salutary effects on other markers. This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin). Change in Biomarker Levels at 24 hours of Milrinone Therapy

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Incidence and severity of cardiotoxicity in metastatic renal cell carcinoma (RCC) patients treated with targeted therapies.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4610 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4610-4610 ◽

Cited By ~ 1

Author(s):

Philip S Hall ◽

Ronald Witteles ◽

Sandy Srinivas ◽

Lauren Christine Harshman

Keyword(s):

Heart Failure ◽

Targeted Therapies ◽

Troponin I ◽

Hypoxia Inducible Factor ◽

Severe Heart Failure ◽

Mtor Inhibitors ◽

Left Ventricular ◽

Close Monitoring ◽

Cardiovascular Toxicity ◽

Asymptomatic Patients

4610 Background: Almost all patients with advanced RCC are treated with therapies targeting the hypoxia inducible factor axis. The potential for these agents to cause cardiovascular (CV) toxicity has been increasingly recognized but the overall incidence and extent have not been well described. We sought to identify and characterize the incidence and severity of CV toxicity among RCC patients treated with targeted therapies. Methods: Between 2004 and 2011, all RCC patients treated with targeted therapies directed against the VEGF or mTOR axes were identified at our institution. The incidence of hypertension, left ventricular (LV) dysfunction, changes in serum markers of CV toxicity (e.g., troponin I, NT-proBNP) and heart failure were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE v.4.0). Results: Cardiovascular toxicity developed in 116 of 159 patients (73%). Excluding hypertension, 52 of 159 (33%) developed cardiovascular toxicity. Cardiac toxicity ranged from asymptomatic drops in LV ejection fraction (LVEF) to rises in NT-proBNP to severe heart failure. Asymptomatic cardiotoxicity as defined by decrease in LVEF or increase in NT-proBNP occurred in 43 patients (27%). Symptomatic heart failure (grade 2-3) and grade 3-4 decrease in LVEF each occurred in 4%. Sunitinib was the most frequently used and most common offending agent, with 66 of 101 sunitinib-treated patients (65%) developing a form of CV toxicity, or 32 of 101 (32%) excluding hypertension. However, it was notable that CV toxicity was observed in 68%, 66%, and 51% of patients treated with bevacizumab, sorafenib, and pazopanib as well. The mTOR inhibitors elicited significantly less CV toxicity, but sample sizes were small. Conclusions: Cardiovascular toxicity is an important adverse event related to targeted therapy administration. Close monitoring for the development of CV toxicity with the use of these agents should become standard of care as early detection of asymptomatic patients could preempt symptomatic toxicity and reduce treatment-related morbidity and mortality.

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Cardiac troponin I as diagnostic and prognostic marker in severe heart failure

The Journal of Heart and Lung Transplantation ◽

10.1016/s1053-2498(00)00120-0 ◽

2000 ◽

Vol 19 (7) ◽

pp. 644-652 ◽

Cited By ~ 132

Author(s):

Luigi La Vecchia ◽

Gabriella Mezzena ◽

Luisa Zanolla ◽

Mariemma Paccanaro ◽

Leonardo Varotto ◽

...

Keyword(s):

Heart Failure ◽

Prognostic Marker ◽

Cardiac Troponin ◽

Troponin I ◽

Severe Heart Failure ◽

Cardiac Troponin I

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Cardiac Troponin I C-Terminal Mutations (K178E and K179E) Cause Severe Heart Failure and Early Mortality in Transgenic Mice

Biophysical Journal ◽

10.1016/j.bpj.2011.11.3050 ◽

2012 ◽

Vol 102 (3) ◽

pp. 560a ◽

Cited By ~ 1

Author(s):

Pierre-Yves Jean-Charles ◽

Yuejin Li ◽

Changlong Nan ◽

Nariman Gobara ◽

Xupei Huang

Keyword(s):

Heart Failure ◽

Transgenic Mice ◽

Cardiac Troponin ◽

Troponin I ◽

Severe Heart Failure ◽

Early Mortality ◽

Cardiac Troponin I

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Acute Heart Failure in a Healthy Young Patient after Severe Carbon Monoxide Poisoning

European Journal of Case Reports in Internal Medicine ◽

10.12890/2019_001340 ◽

2019 ◽

Author(s):

Christos E Lampropoulos ◽

Evagelia Sklavou ◽

Charalampos Anastogiannis ◽

Vasiliki Papanikolaou ◽

Dimitris Tsilivarakis ◽

...

Keyword(s):

Heart Failure ◽

Carbon Monoxide ◽

Troponin I ◽

Carbon Monoxide Poisoning ◽

Severe Heart Failure ◽

Left Ventricular ◽

Co Poisoning ◽

Jugular Veins ◽

X Ray ◽

Cellular Hypoxia

Introduction: Carbon monoxide (CO) poisoning may cause severe cellular hypoxia. Materials and methods: A 28-year-old male presented reduced levels of consciousness and dyspnoea after CO exposure. Clinical examination revealed tachypnoea, bilateral rales, dilated jugular veins and confusion. Troponin I, lactate and carboxyhaemoglobin levels were increased. Thoracic X-ray depicted pulmonary oedema and an echocardiogram, severe heart failure (HF; EF<25%). He was intubated due to clinical deterioration. Results: He remained intubated for 5 days with excellent improvement of left ventricular function (EF>55%). He was discharged 1 week later with full recovery. Discussion: Acute HF is a rare serious complication of CO poisoning, even in healthy young individuals.

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Abstract 843: Restrictive Cardiomyopathy Linked cTnI Mutation (K178E) Causes Severe Heart Failure and Early Mortality

Circulation ◽

10.1161/circ.118.suppl_18.s_623-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Pierre-Yves Jean-Charles ◽

Jianfeng Du ◽

Yuejin Li ◽

Nariman Gobara ◽

Xupei Huang

Keyword(s):

Heart Failure ◽

Transgenic Mice ◽

Diastolic Dysfunction ◽

Troponin I ◽

Severe Heart Failure ◽

Restrictive Cardiomyopathy ◽

Left Ventricular ◽

Early Mortality ◽

Cardiac Contraction ◽

Actin Binding

Multiple mutations in cardiac troponin I (cTnI) have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. Among them, K178E mutation has the worst clinical phenotype. K178E mutation may influence the inhibitory function through actin binding since previous studies have shown that amino acids number 173–181 bind to actin and increase the inhibitory effect of TnI. We modeled the mutation of lysine 178→glutamate (K178E) in human cTnI by cardiac specific expression of the mutated protein (cTnI 179Glu in mouse sequence) in transgenic mice. Multiple lines were generated with varying degrees of expression to establish a dose relationship. Increased resting tension in isolated cardiac myocytes and decreased myofibrillar compliance were the main manifestations in cellular function measurements. In vivo cardiac function measured by high-resolution ultrasonic imaging and Doppler echocardiography revealed a significant diastolic dysfunction characterized with decrease of left ventricular end diastolic dimension (LVEDD), decreased cardiac ejection fraction (EF) and left ventricular faction of shortening (FS) as well as a decreased cardiac output (CO). Doppler measurements showed a restrictive left ventricular filling pattern, i.e. reversed E/A ratio; decreased deceleration time (DT); decreased isovolumic relaxation time (IVRT). Enlarged left and right atria was a dramatic sign, which was observed in most of the transgenic mice, and was developed early and fast (at age of 2–3 weeks). Severely affected lines developed a pathology similar to that observed in human restrictive cardiomyopathy patients who carry the same mutation and with a high early mortality. Our data indicate the causality of this mutation for diastolic dysfunction and heart failure and provide a useful animal model for further understanding the thin filament structure-function relationships and the physiological function of triponin in cardiac contraction and relaxation. (Supported by NIH GM073621 and AHA0715116B) This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).

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