Assessment of biomarkers and clinical parameters as predictors of survival in patients with chagasic heart failure.

BACKGROUND: Chagas disease, endemic in Latin America and spreading globally due to emigration, has a significant health burden, particularly in relation to chagasic heart failure (HF). Chagasic cardiomyopathy (CCM) is characterized by chronic inflammatory myocardial disease. This study aimed to identify inflammatory parameters and biomarkers that could aid in the management of patients with chagasic HF. METHODS AND FINDINGS: A cohort study was conducted at a tertiary cardiology single-center over a mean follow-up period of 2.4 years. The study included patients with HF secondary to CCM enrolled between October 2013 and July 2017. Various clinical parameters, echocardiography findings, parasitemia status, brain natriuretic peptide (BNP) and troponin T (TnT) levels, and inflammatory biomarkers (IL-6, IL-10, IL-12p70, IL-17A, adiponectin, and IFN-γ) were assessed. The study encompassed a cohort of 103 patients, with a median age of 53 years and 70% being male. The left ventricular ejection fraction (LVEF) was 28%, with 40% of patients classified as NYHA II functional class. The median BNP level was 291 pg/ml. The observed mortality rate during the study period was 38.8%. Predictors of lower survival were identified as elevated levels of BNP, TnT, reduced LVEF, and increased adiponectin (thresholds: BNP > 309 pg/ml, TnT > 27.5 ng/ml, LVEF < 25.5%, adiponectin > 38 µg/mL). Notably, there was no evidence indicating a relationship between parasitemia and the inflammatory parameters with lower survival in these patients, including INF-γ, IL-6, IL-10, IL12-(p70), and IL17a. CONCLUSION: Despite the presence of a chronic inflammatory process, the evaluated inflammatory biomarkers in this cohort were not predictive of survival in patients with chagasic HF with reduced ejection fraction (HFrEF). However, reduced LVEF, elevated BNP, adiponectin levels, and troponin T were identified as predictors of lower survival in these patients.

Coronavirus disease-2019 and heart: assessment of troponin and cardiovascular comorbidities as prognostic markers in patients hospitalized with coronavirus disease-2019 in a tertiary center in Brazil.

OBJECTIVE: Our study aimed to evaluate the correlation of cardiac troponin T levels with comorbidities and in-hospital outcomes in patients with coronavirus disease-2019 in Brazil. METHODS: Data from a cohort of 3,596 patients who were admitted with suspected coronavirus disease-2019 in a Brazilian tertiary center, between March and August 2020, were reviewed. A total of 2,441 (68%) patients had cardiac troponin T determined in the first 72 h of admission and were stratified into two groups: elevated cardiac troponin T (cardiac troponin T >0.014 ng/mL) and normal cardiac troponin T. Associations between troponin, comorbidities, biomarkers, and outcomes were assessed. Regression models were built to assess the association of several variables with in-hospital mortality. RESULTS: A total of 2,441 patients were embraced, of which 924 (38%) had normal cardiac troponin T and 1,517 (62%) had elevated cardiac troponin T. Patients with elevated cardiac troponin T were older and had more comorbidities, such as cardiovascular disease, hypertension, diabetes, arrhythmia, renal dysfunction, liver disease, stroke, cancer, and dementia. Patients with abnormal cardiac troponin T also had more altered laboratory parameters on admission (i.e., leukocytes, C-reactive protein, D-dimer, and B-type natriuretic peptide), as well as more need for intensive care unit, vasoactive drugs, mechanical ventilation, dialysis, and blood transfusion. All-cause mortality was markedly higher among patients with increased cardiac troponin T (42 vs. 16%, P<0.001). Multiple regression analysis demonstrated that in-hospital mortality was not independently associated with troponin elevation. CONCLUSION: This study showed that cardiac troponin T elevation at admission was common and associated with several comorbidities, biomarkers, and clinical outcomes in patients hospitalized with coronavirus disease-2019, but it was not an independent marker of in-hospital mortality.

Diagnostic and Cost Efficiency of the 0-h/1-h Rule-out and Rule-in Algorithm for Patients With Chest Pain in the Emergency Department.

BACKGROUND: This study investigated the economic impact of the European Society of Cardiology (ESC) clinical practice guideline recommendation of using the 0-h/1-h rule-out and rule-in algorithm with high-sensitivity cardiac troponin assays (0/1-h algorithm) to triage patients presenting with chest pain.Methods and Results: This post hoc cost-effectiveness evaluation (DROP-ACS; UMIN000030668) used deidentified electronic medical records from health insurance claims from 2 diagnostic centers in Japan. A cost-effectiveness analysis was conducted with 472 patients with care provided following the 0/1-h algorithm (Hospital A) and 427 patients following point-of-care testing (Hospital B). The clinical outcome of interest was all-cause mortality or subsequent myocardial infarction within 30 days of the index presentation. The sensitivity and specificity for the clinical outcome were 100% (95% confidence interval [CI] 91.1-100%) and 95.0% (95% CI 94.3-95.0%), respectively, in Hospital A and 92.9% (95% CI 69.6-98.7%) and 89.8% (95% CI 89.0-90.0%), respectively, in Hospital B. If the diagnostic accuracy of the 0/1-h algorithm was implemented in Hospital B, it is expected that the number of urgent (<24-h) coronary angiograms would decrease by 50%. Incorporating this assumption, implementing the 0/1-h algorithm could potentially reduce medical costs by JPY4,033,874 (95% CI JPY3,440,346-4,627,402) in Hospital B (JPY9,447 per patient; 95% CI JPY 8,057-10,837 per patient). CONCLUSIONS: The ESC 0/1-h algorithm was efficient for risk stratification and for reducing medical costs.

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.

AIMS: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. METHODS AND RESULTS: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). CONCLUSION: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. CLINICAL TRIAL REGISTRATION: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Cost-effectiveness of a high-sensitivity cardiac troponin T systematic screening strategy compared with usual care to identify patients with peri-operative myocardial injury after major noncardiac surgery.

BACKGROUND: About 300 million surgeries are performed worldwide annually and this figure is increasing constantly. Peri-operative myocardial injury (PMI), detected by cardiac troponin (cTn) elevation, is a common cardiac complication of noncardiac surgery, strongly associated with short- and long-term mortality. Without systematic peri-operative cTn screening, most cases of PMI may go undetected. However, little is known about cost effectiveness of a systematic PMI screening strategy with high-sensitivity cardiac troponin T (hs-cTnT) after noncardiac surgery. OBJECTIVE: To assess, in patients with high cardiovascular risk, the cost-effectiveness of a systematic screening strategy using a hs-cTnT assay, to identify patients with PMI after major noncardiac surgery, compared with usual care. DESIGN: Cost-effectiveness analysis; single centre prospective cohort study. SETTING: Spanish University Hospital. PATIENTS: From July 2016 to March 2019, we included 1477 consecutive surgical patients aged ≥65 or if <65, with documented history of cardiovascular disease or impaired renal function, who underwent major noncardiac surgery and required at least an overnight hospital stay. We excluded patients aged <65 years without cardiovascular disease, undergoing minor surgery, or with an expected <24 h hospital stays. INTERVENTIONS: We conducted a decision-tree analysis, comparing a systematic screening strategy measuring hs-cTnT before surgery, and at the 2nd and 3rd days after surgery vs. a usual care strategy. We considered a third-party payer perspective and the outcomes of both strategies in the short-term (30 days follow-up). Information about costs was expressed in Euros-2021. We calculated the incremental cost-effectiveness ratio (ICER) of the systematic hs-cTnT strategy, defined as the expected cost per any additional PMI detected, and explored the robustness of the model using deterministic and probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: ICER of the systematic hs-cTnT screening strategy. RESULTS: The ICER was €425 per any additionally detected PMI. The deterministic sensitivity analysis showed that a 15% variation in costs, and a 1% variation in the predictive values, had a minor impact over the ICER, except in case of the negative predictive value of the systematic hs-cTnT screening strategy. Monte Carlo simulations (probabilistic sensitivity analysis) showed that systematic hs-cTnT screening would be cost-effective in 100% of cases with a 'willingness to pay' of €780. CONCLUSIONS: Our results suggest that systematic peri-operative PMI screening with hs-cTnT may be cost-effective in the short-term in patients undergoing major noncardiac surgery. Economic evaluations, with a long-term horizon, are still needed. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03438448.

Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure With Reduced Ejection Fraction: The VICTORIA Biomarker Substudy.

BACKGROUND: Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect. METHODS AND RESULTS: High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14-1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed. CONCLUSIONS: hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.

Asymptomatic myocardial injury identified on postoperative troponin testing after open or endovascular surgical procedures is a predictor of mortality.

OBJECTIVE: Elevated troponin (TnT) levels after open or endovascular surgical procedures have been previously shown to correlate with significantly higher postoperative and short-term mortality. The incidence of asymptomatic myocardial injury after vascular surgical procedures has also been shown to be high. The aim of the present study was to evaluate the utility of routine postoperative TnT screening and long-term outcomes for patients with postoperative TnT elevation. METHODS: Data from consecutive patients who had undergone open or endovascular surgery on an emergent or elective basis with routine postoperative TnT testing from January 2010 to December 2012 were retrospectively analyzed. Elevated postoperative TnT was considered >0.01 ng/mL. Patients with no documented postoperative TnT levels, those who had denied research authorization, and those with elevated TnT levels secondary to renal insufficiency alone were excluded. Patients were also excluded if they had required a dialysis access procedure, varicose vein procedure, or any procedure performed on an outpatient basis, because these were considered nonmajor surgeries. The end points were all-cause mortality at 30 days and 1, 2, 4, and 8 years postoperatively. Mortality data were retrieved from the electronic medical records and the Social Security Death Index and Accurint Death database. RESULTS: During the 3-year study period, 1632 patients with postoperative TnT levels available had met the inclusion criteria (70% men; 30% women; mean age, 69.7 years). Postoperatively, 410 patients (25.1%) had had elevated TnT levels (TnT+) and 1222 (74.9%) had had nonelevated TnT levels (TnT-). Of the 410 TnT+ patients, 261 had undergone open, 143 had undergone endovascular, and 6 had undergone hybrid procedures. These included 180 aortic, 128 infrainguinal, 22 cerebrovascular, and 80 upper extremity or miscellaneous procedures. Of the 410 TnT+ patients, 168 had experienced asymptomatic myocardial injury. The 30-day mortality was significantly higher for the TnT+ patients than for the TnT- patients (3.9% vs 0.8%; P < .001). The cumulative probability of death for the TnT+ patients remained significantly higher than that for the TnT- patients at 1 (13% vs 3.2%), 2 (17.8% vs 4.8%), 4 (43% vs 18.5%), and 8 (81.4% vs 48.6%) years (P < .0001). The difference held true even for the 168 asymptomatic TnT+ patients compared with the TnT- patients at 30 days (2.4% vs 0.8%) and 1 (7.6% vs 3.2%), 2 (13.3% vs 4.8%), 4 (43.6 vs 18.5%) and 8 (80.8 vs 48.6%) years (P < .0001). CONCLUSIONS: In the present study, patients with elevated TnT levels after vascular surgery had had significantly higher early and late all-cause mortality compared with those with normal postoperative TnT levels. This was true even for patients with asymptomatic TnT elevation, suggesting a role might exist for routine postoperative TnT screening to allow for long-term risk stratification and targeted medical management.

Cost-effectiveness of a rule-out algorithm of acute myocardial infarction in low-risk patients: emergency primary care versus hospital setting.

AIMS: Hospital admissions of patients with chest pain considered as low risk for acute coronary syndrome contribute to increased costs and crowding in the emergency departments. This study aims to estimate the cost-effectiveness of assessing these patients in a primary care emergency setting, using the European Society of Cardiology (ESC) 0/1-h algorithm for high-sensitivity cardiac troponin T, compared to routine hospital management. METHODS: A cost-effectiveness analysis was conducted. For the primary care estimates, costs and health care expenditure from the observational OUT-ACS (One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome) study were compared with anonymous extracted administrative data on low-risk patients at a large general hospital in Norway. Patients discharged home after the hs-cTnT assessment were defined as low risk in the primary care cohort. In the hospital setting, the low-risk group comprised patients discharged with a non-specific chest pain diagnosis (ICD-10 codes R07.4 and Z03.5). Loss of health related to a potential increase in acute myocardial infarctions the following 30-days was estimated. The primary outcome measure was the costs per quality-adjusted life year (QALY) of applying the ESC 0/1-h algorithm in primary care. The secondary outcomes were health care costs and length of stay in the two settings. RESULTS: Differences in costs comprise personnel and laboratory costs of applying the algorithm at primary care level (€192) and expenses related to ambulance transports and complete hospital costs for low-risk patients admitted to hospital (€1986). Additional diagnostic procedures were performed in 31.9% (181/567) of the low-risk hospital cohort. The estimated reduction in health care cost when using the 0/1-h algorithm outside of hospital was €1794 per low-risk patient, with a mean decrease in length of stay of 18.9 h. These numbers result in an average per-person QALY gain of 0.0005. Increased QALY and decreased costs indicate that the primary care approach is clearly cost-effective. CONCLUSION: Using the ESC 0/1-h algorithm in low-risk patients in emergency primary care appears to be cost-effective compared to standard hospital management, with an extensive reduction in costs and length of stay per patient.

Assessment of Acute Rejection by Global Longitudinal Strain and Cardiac Biomarkers in Heart-Transplanted Patients.

Aims: The aim of this study was to evaluate left ventricular global longitudinal strain (LVGLS), N-terminal pro brain natriuretic peptide (Nt-ProBNP), and Troponin T as non-invasive markers for acute cellular rejection (ACR) diagnosis and severity assessment after heart transplantation (HTx). Methods: We retrospectively included all HTx patients transplanted from 2013 to 2019. At each visit, the patients were subjected to endomyocardial biopsy (EMB), measurement of Nt-ProBNP and Troponin T, and protocoled echocardiography with assessment of LVGLS. Sudden drop in graft function (SDGF) was defined as a drop in LVGLS ≥-2% in combination with either an increase in Troponin T ≥20% or Nt-ProBNP ≥30% compared with levels at the latest visit. Results: We included 1,436 EMBs from 83 HTx patients. The biopsies were grouped as 0R (n = 857), 1R (n = 538), and ≥2R (n = 41). LVGLS was lower and Troponin T and Nt-ProBNP higher in the 2R group than in the 0R and 1R groups (LVGLS: -12.9 ± 3.8% versus -16.9 ± 3.1% and -16.1 ± 3.3%; Troponin T: 79 [33;230] ng/l versus 27 [13;77] ng/l and 27 [14;68] ng/l; Nt-ProBNP: 4,174 [1,095;9,510] ng/l versus 734 [309;2,210] ng/l and 725 [305;2,082], all p < 0.01). A SDGF was seen at 45 visits of which 19 had ≥2R ACR. EMBs showed ACR in 20 cases without SDGF. Finally, neither was SDGF seen nor did the EMB show rejection in 1,136 cases. Thus, the sensitivity of SDGF for ≥2R ACR detection was 49% (32-65) and specificity 98% (97-99). The positive predictive value (PPV) was 42% (31-55) and the negative predictive value (NPV) 98% (98-99). The diagnostic value improved in a sub-analysis excluding EMBs within 3 months after HTx, clinically interpreted false positive ≥2R ACR cases, and cases with ≥2R ACR who recently (<2 weeks) were treated with intravenous methylprednisolone due to ≥2R ACR (sensitivity 75% (48-93), specificity 97% (96-98), NPV 99% (99-100), and PPV 39% (27-52). Conclusions: Patients with ≥2R ACR have lower LVGLS and higher Troponin T and Nt-ProBNP than patients without 2R rejection. A non-invasive model combining changes in LVGLS and Troponin T or Nt-ProBNP showed excellent negative predictive value and moderate sensitivity and may be used as a gatekeeper to invasive biopsies after HTx.

Serial Assessment of Myocardial Injury Markers in Mechanically Ventilated Patients With SARS-CoV-2 (from the Prospective MaastrICCht Cohort).

Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (ß -0.93 [-1.37; -0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (ß -0.08 [-0.11; -0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.

Assessment of COVID-19 deaths from cardiological perspective.

BACKGROUND: COVID-19 can cause a variety of cardiac complications and a range of electrocardiographic abnormalities. We analysed cardiological parameters including ECG and high-sensitivity troponin T (hs-TnT) level and their association with mortality in hospitalised patients with COVID-19. METHODS: We retrospectively analysed the demographics, comorbidities, laboratory findings and electrocardiographic parameters of 453 consecutive patients, whose outcome was clear, died or discharged. Findings were compared between survivors and non-survivors. Also, the same comparison was made between cardiac injury and no-cardiac injury subgroups. RESULTS: The cardiac injury group had significantly higher in-hospital mortality than the no-cardiac injury group. Also, frequencies of atrial fibrillation, axis change, ST-segment/T-wave change, fragmented QRS, premature atrial/ventricular contraction was found to be higher in the cardiac injury group. Moreover, non-survivors had longer QRS intervals, more frequent ST-segment/T-wave changes and isolated S1Q3T3 pattern than surviving patients. Laboratory results showed median values of hs-TnT at the admission of 4.95 ng/L (IQR, 3-12.35) with concentrations markedly higher in the non-surviving patients vs survivors. Hs-TnT value along with age and respiratory rate was found to be an independent predictor of in-hospital mortality in hospitalised patients with COVID-19. Comorbidities were more frequently reported in non-surviving and cardiac injury groups than those surviving and without cardiac injury. CONCLUSIONS: In COVID-19 patients, both elevated hs-TnT and ECG abnormalities, suggesting cardiac involvement, on admission portends an ominous prognosis and indicates at higher risk of in-hospital mortality. Prioritised treatment and more aggressive therapeutic strategies could be planned to avoid the occurrence of death in these patients.

The value of perioperative biomarker release for the assessment of myocardial injury or infarction in cardiac surgery.

OBJECTIVES: Cardiac biomarkers are indicators of irreversible cell damage. Current myocardial infarction (MI) definitions require concomitant clinical characteristics. For perioperative MI, a correlation of biomarker elevations and mortality has been suggested. Definitions emerged relying on cardiac biomarker release only. This approach is questionable as several clinical and experimental scenarios exist where relevant biomarker release can occur apart from MI. METHODS: We reviewed the clinical and basic science literature and revealed important aspects regarding the use and interpretation of cardiac biomarker release with special focus on their interpretation in the perioperative setting. RESULTS: Ischaemic biomarkers may be released without cell death in multiple conditions, such as after endurance runs in athletes, temporary inotropic stimulation in animal models and flow variations in in vitro cell models. In addition, access through atrial tissue during cannulation or concomitant valve procedures adds sources of enzyme release that may not be related to ventricular ischaemia (i.e. MI). Such non-cell death-related mechanisms may explain the lack of poor correlations of enzyme release and long-term outcomes in recent trials. In addition, the 3 main biomarkers, troponin T, I and creatine kinase myocardial band, differ in their release kinetics, which may differentially trigger MI events in trial patients. CONCLUSIONS: The identification of irreversible myocardial injury in cardiac surgery based only on biomarker release is unreliable. Cell death- and non-cell death-related mechanisms create a mix in the perioperative setting that requires additional markers for proper identification of MI. In addition, the 3 most common ischaemic biomarkers display different release kinetics adding to the confusion. We review the topic.

High-Sensitivity Troponin T For The Risk Assessment Of Patients With Acute Atrial Fibrillation.

Elevations of high-sensitivity troponin T (Hs-TnT) in the setting of acute atrial fibrillation (AF) are not clearly understood. This study evaluated factors associated with these elevations and its prognostic implication. We prospectively included 413 consecutive patients who presented to our institution with acute AF. The median Hs-TnT on admission was 12 ng/l and 39.4% had values above the 99th percentile. At 1-year, AF recurrence occurred in 38.3% of patients, and MACE in 5.6%. Hs-TnT levels were not associated with AF reversion (p 0.869) or with 1-year AF recurrence (p 0.132) but they were with MACE (12 vs 24 ng/l, p 0.001). Thus, Hs-TnT was a strong predictor of MACE (HR 3.486, 95% CI 1.256-5.379, p 0.009) in this population. In conclusion, Hs-TnT elevation was frequently observed in patients with acute AF, and although it was not associated with AF reversion or recurrence, it was highly predictive of MACE at 1-year.

Multimodal assessment of acute cardiac toxicity induced by thoracic radiotherapy in cancer patients. Study protocol.

BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Assessment of Prognostic Value of High-Sensitivity Cardiac Troponin T for Early Prediction of Chemoradiation Therapy-Induced Cardiotoxicity in Patients with Non-Small Cell Lung Cancer: A Secondary Analysis of a Prospective Randomized Trial.

PURPOSE: Cardiotoxicities induced by cancer therapy can negatively affect quality of life and survival. We investigated whether high-sensitivity cardiac troponin T (hs-cTnT) levels could serve as biomarker for early detection of cardiac adverse events (CAEs) after chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This study included 225 patients who received concurrent platinum and taxane-doublet chemotherapy with thoracic radiation therapy to a total dose of 60 to 74 Gy for NSCLC. All patients were evaluated for CAEs; 190 patients also had serial hs-cTnT measurements. RESULTS: Grade ≥3 CAEs occurred in 24 patients (11%) at a median interval of 9 months after CRT. Pretreatment hs-cTnT levels were higher in men, in patients aged ≥64 years, and in patients with pre-existing heart disease or poor performance status (P < .05). hs-cTnT levels increased at 4 weeks during CRT (P < .05) and decreased after completion of CRT but did not return to pretreatment levels (P = .002). The change (Δ) in hs-cTnT levels during CRT correlated with mean heart dose (P = .0004), the heart volumes receiving 5 to 55 Gy (P < .05), and tumor location (P = .006). Risks of severe CAEs and mortality were significantly increased if the pretreatment hs-cTnT was >10 ng/L or the Δ during CRT was ≥5 ng/L. CONCLUSIONS: Elevation of hs-cTnT during CRT was radiation heart dose-dependent, and high hs-cTnT levels during the course of CRT were associated with CAEs and mortality. Routine monitoring of hs-cTnT could identify patients who are at high risk of CRT-induced CAEs early to guide modifications of cancer therapy and possible interventions to mitigate cardiotoxicity.