Early Detection Of Cardiac Damage Research Articles

Cardiac Biomarkers and Biochemical Changes in Cattle with Traumatic Pericarditis

Traumatic pericarditis (TP) emerges as a result of foreign bodies pricking the heart, and these animals cannot be treated. Traumatic pericarditis is one of the most important cardiac diseases that may result in a decrease in milk yield, animal death, and fetal deaths in affected pregnant animals and lead to economic losses. Cardiac markers, which have been used in human medicine for years and have recently started to be used in veterinary medicine, can detect mild myocardial damage that may occur in the early stages of heart-related diseases. In this study it was aimed to determine the cardiac damage in cattle with TP by cardiac biomarkers. In the study, cTn-I, ANP, NT-proBNP, homocysteine, CRP, CK-MB, LDH, AST, and ALT levels were determined to be statistically higher in cattle with TP than in healthy animals (P < 0.01). NT-proBNP increased approximately 11 times, ANP about 10 times, cTn-I and Homocysteine increased 3 times, and CRP and CK-MB increased 2 times in cattle with TP. In conclusion, some cardiac markers were examined in the early detection of cardiac damage and diagnosis of cattle with TP, and it was concluded that the use of these markers would be beneficial. Moreover, it was concluded that ANP, Nt-proBNP, and homocysteine, which were the first data on cattle with TP, could be used in the detection of the severity of cardiac damage.

Usefulness of Global Longitudinal Strain-Guided Management in Preventing Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitor-Induced Myocardial Damage.

Background: Trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is a specific first-line treatment for patients with HER2-positive cancers. Cardiac dysfunction is among the most problematic adverse events associated with trastuzumab. Although regular echocardiographic screening is recommended for early detection of cardiac damage, few reports have investigated the validity of echocardiographic screening in chemotherapy. Therefore, the aim of this study was to determine whether a GLS-guided management approach could reduce cardiotoxicity and discontinuation of trastuzumab chemotherapy. Methods and Results: To evaluate the usefulness of global longitudinal strain (GLS)-guided cardioprotective interventions, we retrospectively analyzed 67 patients treated with trastuzumab who underwent structured echocardiographic assessments before and after 1, 3, and 6 courses of trastuzumab administration. If a >15% relative decrease in GLS was identified, cardioprotective agents were administered. Thirty (44.8%) patients had breast cancer; the remaining patients had salivary gland cancer. The median observation period for the intervention group was 304 days from the initial evaluation. Nineteen (28.4%) patients exhibited a >15% relative decrease in GLS, and consequently received cardioprotective agents. The incidence of trastuzumab discontinuation for cardiogenic reasons was significantly lower among patients receiving GLS-guided interventions than among those not receiving the intervention (2.4% vs. 24.0%; P=0.009). The incidence of a subsequent decline in left ventricular ejection fraction was lower among patients receiving the intervention than among those not receiving the intervention (4.8% vs. 24.0%; P=0.04). Conclusions: GLS-guided cardioprotective intervention significantly decreased the incidence of trastuzumab discontinuation.

Early Detection of Cardiac Damage by Two-Dimensional Speckle Tracking Echocardiography After Thoracic Radiation Therapy: Study Protocol for a Prospective Cohort Study.

BackgroundAs one of the important treatment methods for cancer patients, radiotherapy may lead to incidental irradiation of the heart, resulting in radiotherapy-induced heart disease (RIHD) arising many years after radiotherapy. While, there are few studies on early subclinical cardiac damage, which may be essential for the protection of late RIHD. To detect and predict RIHD and early subclinical cardiac damage induced by thoracic radiation therapy, based on two-dimensional speckle tracking echocardiography (2D STE) combined with multiple circulating biomarkers and accurate heart dosimetry.Methods and AnalysisThis is a monocentric prospective cohort study in which 104 patients treated for malignant tumors and with cardiac radiation exposure will be included. All participants will be followed for 12 months after radiotherapy. Echocardiography, 2D STE, and blood samples will be underwent at 5-time points (baseline; after completion of RT; 2, 6, and 12 months after RT). Left ventricular ejection fraction (LVEF); global longitudinal, radial, and circumferential strain; diastolic function parameters; creatine kinase (CK); creatine kinase isoenzyme (CK-MB); cardiac troponin T (cTnT); N-terminal pro-B-type natriuretic peptide (NT-proBNP) and hypersensitive C-reactive protein (hs-CRP) will be measured at baseline and every follow-up time. The incidence of major adverse cardiovascular events will be recorded.DiscussionThis study details the protocol and presents the primary limits and advantages of this single-center project. The inclusion of patients began in 2021, and the results are expected to be published in 2023. This study will be allowed to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction induced by thoracic radiation therapy, based on two-dimensional speckle tracking echocardiography (2D STE) combined with circulating biomarkers and accurate heart dosimetry. Furthermore, we will evaluate risk factors of subtle cardiac damage and identify high-risk groups for early heart damage.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04443400.

Heart rate response and chronotropic incompetence during cardiopulmonary exercise testing in childhood acute lymphoblastic leukemia survivors

Cardiopulmonary exercise tests (CPET) focusing on analyses of heart rate (HR) responses and chronotropic incompetence (CI) could provide early information about treatment’s negative cardiac effects. We examined childhood acute lymphoblastic leukemia (ALL) survivors’ HR response during maximal CPET and identified survivors with CI. A total of 250 childhood ALL survivors underwent a CPET on ergocycle to assess their HR response. We used a multiparametric structure of three methods to assess survivors’ CI, as follows: 1) age-predicted HRmax (APMHR): failure to achieve 85% of the APMHR at the peak of CPET; 2) HR reserve (HRR): failure to achieve 80% of the HRR at the peak of CPET; and 3) metabolic chronotropic relationship (MCR): failure to reach an MCR slope ratio >0.8 at each stage of the CPET. Among 250 childhood ALL survivors, 216 survivors performed a maximum CPET. We observed that 73 males and 74 females did not achieve their predicted HRmax. We found that 6 survivors did not achieve 85% of their APMHR (80.9 ± 3.9%) and had an MCR below 80% (53.9 ± 13.8%). In addition, 16 survivors did not achieve 80% of their HRR (71.0 ± 7.4%) and among them, 15 survivors had an MCR below 80% (61.0 ± 12.1%). Survivors with CI had a significantly lower cardiorespiratory fitness than those without CI. This study shows that survivors are at risk of developing altered HR responses and CI many years after the end of their cancer treatments. These findings highlight the importance of early detection of cardiac damage due to cancer treatments.

Evaluation of Cardiac Troponin Level Following Generalized Tonic-Clonic Seizure in Children; Cross-sectional Study

Background: Cardiac troponin I (CTnI) is recognized as a proper marker for early detection of cardiac damage. Generalized tonic-clonic (GTC) seizures may lead to cardiac ischemia or myocardial injury associated with elevated CTnI. The present study aimed at evaluating the level of CTnI in children with status GTC seizures. Methods: 50 patients with GTC seizures and a normal cardiac function referred to Amirkabir Hospital, Arak, Iran were evaluated. The medical history of all patients was taken, and clinical examinations were performed. For all patients were performed Serum CTnI measurements, electroencephalography (EEG), electrocardiography (ECG), and echocardiography. Results: The patients’ mean age was 7.80 ± 4.01 years and 26 (52%) children were female (female: male ratio, 1.08). the mean duration of seizure was 31.54 ± 1.56 minutes. Abnormal EEG patterns were documented in 83 (86%) patients, while abnormal CT scan was not found in any of the patients. The mean level of CTnI was at the high end of the range in patients (57.02 ± 10.80 ng/mL). There was a positive correlation between serum CTnI and age (P = 0.001, R = 0.492). Also, the serum level of CTnI was significantly correlated with the onset of GTC seizure (R = 0.004, P = 0.001). Conclusion: The serum CTnI level exceeded the normal level in children with seizures. Therefore, cardiac monitoring of patients with status GTC seizures may be helpful in the ictal and postictal phases for evaluating cardiac injury, especially in children with risk factors for coronary diseases, such as Kawasaki disease, cardiomyopathy, or coronary anomalies.

The role of human heart-type Fatty Acid Binding Protein in the early detection of myocardial injury in Acute Coronary Syndrome

Objectives: To evaluate the use of H-FABP as a novel marker in early detection of cardiac damage (MI) in patients presenting with symptoms of acute coronary syndrome (ACS). Methods: This cross-sectional study included 250 subjects; 125 patients of ACS presenting within four hours of the onset of chest pain and/dyspnea and 125 age and sex-matched healthy controls. An initial blood sample was taken from patients at presentation. Blood samples of healthy control subjects were also taken. The blood samples of both groups were centrifuged and stored at -200 C for H-FABP analysis. All the patients and control subjects were thoroughly examined and detailed history was taken. The diagnostic test was troponin-T.H-FABP concentrations of all samples were measured by ELISA-kit. The results were analyzed statistically. A p-value≤0.05 was considered statistically significant. Results: In 125 patients of ACS, H-FABP showed a sensitivity of 85% and specificity of 83.3% for acute MI diagnosis at a cut-off level of 16 ng/ml. Positive predictive values and negative predictive values were 96.8% and 48.4% respectively. The accuracy was 84.4%and the area under the ROC curve was 0.842. Conclusion: Evaluation of heart-type fatty acid-binding Protein (H-FABP) within four hours of onset ACS symptoms may be a valuable tool in the diagnosis of AMI. Keywords: Heart-type fatty acid-binding protein, Acute coronary syndrome, Myocardial infarction.

Early myocardial changes induced by doxorubicin in the nonfailing dilated ventricle.

Several studies have demonstrated that administration of doxorubicin (DOXO) results in cardiotoxicity, which eventually progresses to dilated cardiomyopathy. The present work aimed to evaluate the early myocardial changes of DOXO-induced cardiotoxicity. Male New Zealand White rabbits were injected intravenously with DOXO twice weekly for 8 wk [DOXO-induced heart failure (DOXO-HF)] or with an equivolumetric dose of saline (control). Echocardiographic evaluation was performed, and myocardial samples were collected to evaluate myocardial cellular and molecular modifications. The DOXO-HF group presented cardiac hypertrophy and higher left ventricular cavity diameters, showing a dilated phenotype but preserved ejection fraction. Concerning cardiomyocyte function, the DOXO-HF group presented a trend toward increased active tension without significant differences in passive tension. The myocardial GSSG-to-GSH ratio and interstitial fibrosis were increased and Bax-to- Bcl-2 ratio presented a trend toward an increase, suggesting the activation of apoptosis signaling pathways. The macromolecule titin shifted toward the more compliant isoform (N2BA), whereas the stiffer one (N2B) was shown to be hypophosphorylated. Differential protein analysis from the aggregate-enriched fraction through gel liquid chromatography-tandem mass spectrometry revealed an increase in the histidine-rich glycoprotein fragment in DOXO-HF animals. This work describes novel and early myocardial effects of DOXO-induced cardiotoxicity. Thus, tracking these changes appears to be of extreme relevance for the early detection of cardiac damage (as soon as ventricular dilation becomes evident) before irreversible cardiac function deterioration occurs (reduced ejection fraction). Moreover, it allows for the adjustment of the therapeutic approach and thus the prevention of cardiomyopathy progression. NEW & NOTEWORTHY Identification of early myocardial effects of doxorubicin in the heart is essential to hinder the development of cardiac complications and adjust the therapeutic approach. This study describes doxorubicin-induced cellular and molecular modifications before the onset of dilated cardiomyopathy. Myocardial samples from doxorubicin-treated rabbits showed a tendency for higher cardiomyocyte active tension, titin isoform shift from N2B to N2BA, hypophosphorylation of N2B, increased apoptotic genes, left ventricular interstitial fibrosis, and increased aggregation of histidine-rich glycoprotein.

Application of Speckle-Tracking Echocardiography in an Experimental Model of Isolated Subendocardial Damage

The subendocardium is highly vulnerable to damage and is thus affected even in subclinical disease stages. Therefore, methods reflecting subendocardial status are of great clinical relevance for the early detection of cardiac damage and the prevention of functional impairment. The aim of this study was to investigate the potentialability of myocardial strain parameters to evaluate changes within the subendocardium. Male 129/Sv mice were injected with isoproterenol (ISO; n=32) to induce isolated subendocardial fibrotic lesions or saline as appropriate control (n=15). Transthoracic echocardiography was performed using a 30-MHz linear-frequency transducer coupled to a high-resolution imaging system, and acquired images were analyzed for conventional and strain parameters. The degree of collagen content within the different cardiac layers was quantified by histologic analysis and serum levels of tissue inhibitor of metalloproteinase-1, abiomarker for fibrosis, were assessed. ISO treatment induced a marked increase in subendocardial collagen content in response to cell loss (control vs ISO, 0.6±0.3% vs 5.8±0.9%; P<.001) and resulted in a moderate increase in left ventricular wall thickness with preserved systolic function. Global longitudinal peak strain (LS) and longitudinal strain rate were significantly decreased in ISO-treated animals (LS, -15.49% vs -11.49% [P=.001]; longitudinal strain rate, -4.81 vs -3.88sec-1 [P<.05]), whereas radial and circumferential strain values remained unchanged. Global LS was associated with subendocardial collagen content (r=0.46, P=.01) and tissue inhibitor of metalloproteinase-1 serum level (r=0.52, P<.05). Further statistical analyses identified global LS as a superior predictor for the presence of subendocardial fibrosis (sensitivity, 84%; specificity, 80%; cutoff value, -14.4%). Assessment of LS may provide a noninvasive method for the detection of subendocardial damage and may consequently improve early diagnosis of cardiac diseases.

Modern Management of Anthracycline-Induced Cardiotoxicity in Lymphoma Patients: Low Occurrence of Cardiotoxicity with Comprehensive Assessment and Tailored Substitution by Nonpegylated Liposomal Doxorubicin.

Anthracyclines (AC) are still undeniable drugs in lymphoma treatment, despite occasionally causing cardiotoxicity. Liposomal AC may reduce cardiotoxicity while retaining clinical efficacy; also, biomarker monitoring during chemotherapy allows early detection of cardiac damage, enabling strategies to prevent left ventricular ejection fraction (LVEF) deterioration. We conducted a prospective observational trial in a real-life population of lymphoma patients, combining advanced echocardiography and biomarkers (Troponin I [TnI]) for early detection of cardiotoxicity; we applied a prespecified policy to minimize cardiotoxicity, selecting patients with higher baseline risk to replace doxorubicin with nonpegylated liposomal doxorubicin (NPLD) and starting cardioprotective treatment when subclinical cardiotoxicity was detected. Ninety-nine patients received ≥1 cycle of chemotherapy (39 with NPLD): 38 (NPLD = 34) were older than 65 years. At baseline, the NPLD subgroup had more cardiovascular risk factors and comorbidities than the doxorubicin subgroup. After treatment, echocardiographic parameters did not worsen in the NPLD subgroup; significant LVEF reduction occurred in two patients treated with doxorubicin. Over treatment course, TnI rises increased linearly in the doxorubicin subgroup but modestly in the NPLD subgroup. At doxorubicin doses >200 mg/m2 the difference was statistically significant, with more TnI rises in the doxorubicin subgroup. NPLD-treated patients did not experience higher rates of grade 3-4 adverse events. Within the diffuse large B-cell lymphomas category, we observed similar rates of complete and overall responses between doxorubicin- and NPLD-treated patients. A comprehensive strategy to prevent, detect, and treat cardiotoxicity allows an optimal management of the lymphoma with low incidence of cardiac complications. The Oncologist 2017;22:422-431 IMPLICATIONS FOR PRACTICE: Despite the recent advances of targeted therapy in cancer, old cytotoxic drugs such as anthracyclines (AC) still play a fundamental role in the treatment of many lymphoma patients. We tested and validated in a real-life setting a personalized approach to prevent, detect, and treat AC-induced cardiotoxicity; biomarker monitoring was accomplished by Troponin I measurements before and after chemotherapy infusions, allowing detection of early subclinical cardiotoxicity, which was preemptively treated with cardio-protectants (beta blockers and angiotensin-converting-enzyme inhibitors). A telemedicine system allowed interdisciplinary management of the patients with an expert cardiologist. Furthermore, tailored use of liposomal AC following a prespecified policy appeared to prevent the excess cardiotoxicity expected in high-risk patients.

Diastolic Dysfunction Occurs Early in HER2-Positive Breast Cancer Patients Treated Concurrently With Radiation Therapy and Trastuzumab.

Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT). Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified. Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15-D40, D60-D70, and V3-V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone. Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab. Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose-volume of the heart irradiated in patients with left-sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose-volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.

Monitoring of cardiac damage in cancer patients treated with cardiotoxic drugs

In recent years, thanks to advances in early diagnosis and especially to substantial improvements in therapy, there has been a significant increase in the survival of cancer patients. Almost all cancers can be cured today, and survival of patients over 5-10 years is a tangible goal in many types of cancer. Cardiovascular complications are a growing problem in clinical practice that may frustrate modern oncological outcome of therapy. For this reason, a careful evaluation of the patient risk profile through a close collaboration among physicians and careful monitoring of patients are necessary for a successful treatment. Among the most common and dangerous complications of many drugs used in cancer chemotherapy, there is the development of myocardial damage and heart failure. The present review focuses on the type of cancer drugs that may induce cardiac dysfunction and provides the clinical cardiologist monitoring schemes applicable in daily clinical practice aimed at early detection of cardiac damage.

Managing Cardiotoxicity of Chemotherapy

The increase in survivorship of cancer patients makes the understanding of the available options for prevention and treatment of cardiotoxicity induced by antineoplastic agents a crucial topic both for cardiologists and oncologists. The most frequent and typical clinical manifestation of cardiotoxicity is asymptomatic or symptomatic left ventricular dysfunction, which may progress to overt heart failure. It may be induced not only by conventional cancer therapy, like anthracyclines, but also by new antitumoral targeted therapy such as trastuzumab. The current standard for monitoring cardiac damage during antineoplastic treatment, mainly based on the quantification of left ventricular ejection fraction, detects cardiac toxicity only when a functional impairment has already occurred. Evaluation of cardiac biomarkers such as troponin, however, has shown excellent sensitivity in the early detection of cardiotoxicity by the identification of patients with subclinical cardiac injury that precedes the development of cardiac dysfunction. The use of angiotensin-converting enzyme inhibitors in patients with troponin elevation during chemotherapy may be an effective tool to prevent left ventricular ejection fraction reduction and late cardiac events. There are no well established recommendations for treatment of cancer patients who develop cardiac dysfunction. Angiotensin-converting enzyme inhibitors and beta-blockers have proven to be effective in this setting. However, there are concerns in using these medications in cancer patients, and therefore the tendency is to treat patients only if symptomatic. However, the clinical benefit of these medications may be more evident in asymptomatic patients, and the recovery of cardiac function strongly depends on the amount of time elapsed from the end of chemotherapy to the start of heart failure therapy. This observation suggests that the early detection of cardiac damage is crucial and early use of angiotensin-converting enzyme inhibitors and beta-blockers should be considered in patients with left ventricular dysfunction induced by antineoplastic agents.

N-Terminal-proB-Type Natriuretic Peptide as a Marker for Acute Anthracycline Cardiotoxicity in Children

Anthracyclines are widely used in the treatment of pediatric cancer but their use is associated with cardiotoxicity. The cardiotoxic effect may become clinically apparent many years after therapy, and no reliable method exists for early detection of cardiac damage while the patient is receiving the drug. The natriuretic peptides have been established as markers for anthracycline-induced cardiotoxicity in adults and markers for cardiac dysfunction in children. We examined whether N-terminal proB-type natriuretic peptide (NT-proBNP) may be used as a marker for anthracycline-induced cardiotoxicity in children. Twenty-three consecutive pediatric patients with newly diagnosed cancer were enrolled in this study. All patients received anthracycline-containing chemotherapy. Fifty-four age-matched children served as controls. Serial measurements of plasma NT-proBNP levels were taken before and after each anthracycline-containing course. Echocardiograms were performed before initiation of treatment and at the end of the study. Plasma levels of NT-proBNP were within normal limits before treatment and increased significantly only after the first anthracycline dose (from 150+/-112 to 327+/-321 pg/mL, mean+/-SD, P=0.02) and not after subsequent doses. This increase was attributed mainly to a subgroup of patients who received more than 25 mg/m of doxorubicin. In 14 patients (61%), the highest NT-proBNP level occurred after the first anthracycline dose. All patients had normal echocardiograms and none developed heart failure. NT-proBNP increases significantly after the first anthracycline course in a subset of pediatric cancer patients. This increase is not associated with clinical or echocardiographic evidence of cardiac dysfunction. Anthracyclines may be more cardiotoxic in the first course than in subsequent courses. Longer follow-up of these patients is necessary to determine whether NT-proBNP can be used as an early marker for anthracycline-induced cardiotoxicity.

Early Detection of Cardiac Damage With Heart Fatty Acid-Binding Protein After Cardiac Operations

Background. It is still difficult to evaluate myocardial damage in the acute phase of reperfusion in cardiac operations. We investigated the clinical significance of human heart fatty acid-binding protein (HH-FABP) for detecting myocardial damage after cardiac operations earlier than creatine kinase MB isoform or troponin-T. Methods. Blood samples from 20 patients who underwent coronary artery bypass grafting were collected serially after reperfusion to measure serum levels of creatine kinase-MB, troponin-T, and HH-FABP. Results. Serum HH-FABP levels peaked earliest after reperfusion. In addition, the maximum serum HH-FABP level was predictable immediately after reperfusion. The maximum serum HH-FABP level correlated with the maximum serum creatine kinase-MB or troponin-T level, as well as with the aortic cross-clamp time or the maximum dose of catecholamines administered after reperfusion. Conclusions. Measurements of HH-FABP allow for earlier evaluation of myocardial damage in the acute phase of reperfusion. Human heart fatty acid-binding protein may be a useful indicator of myocardial damage after cardiac operations.