scholarly journals Cardiotoxic effects and myocardial injury: the search for a more precise definition of drug cardiotoxicity

2021 ◽  
Vol 59 (1) ◽  
pp. 51-57
Author(s):  
Daniela Maria Cardinale ◽  
Martina Zaninotto ◽  
Carlo Maria Cipolla ◽  
Claudio Passino ◽  
Mario Plebani ◽  
...  

AbstractDrug-induced cardiotoxicity is a major clinical problem; cardiotoxic drugs may induce both cardiac dysfunction and myocardial injury. Several recent studies reported that cardiac troponins measured with high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have some concerns about the standard definition of cardiotoxicity, in particular, regarding the early evaluation of chemotherapy cardiotoxicity in cancer patients. Several recent studies using the hs-cTn assay indicate that myocardial injury may precede by some months or years the diagnosis of heart failure (HF) based on the evaluation of left ventricular ejection fraction (LVEF). Accordingly, hs-cTn assay should considered to be a reliable laboratory test for the early detection of asymptomatic or subclinical cardiotoxic damage in patients undergoing cancer chemotherapy. In accordance with the Fourth Universal Definition of Myocardial Infarction and also taking into account the recent experimental and clinical evidences, the definition of drug-cardiotoxicity should be updated considering the early evaluation of myocardial injury by means of hs-cTn assay. It is conceivable that the combined use of hs-cTn assay and cardiac imaging techniques for the evaluation of cardiotoxicity will significantly increase both diagnostic sensitivity and specificity, and also better prevent chemotherapy-related left ventricular (LV) dysfunction and other adverse cardiac events. However, large randomized clinical trials are needed to evaluate the cost/benefit ratio of standardized protocols for the early detection of cardiotoxicity using hs-cTn assay in patients receiving chemotherapy for malignant diseases.

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ahmed Ayuna ◽  
Nik Abidin

Abstract Background Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. Main body of the abstract PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1–156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. Short conclusion Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bo Hu ◽  
Fei Gao ◽  
Mengwei Lv ◽  
Ban Liu ◽  
Yu Shi ◽  
...  

Abstract Background With the development of cardiac surgery techniques, myocardial injury is gradually reduced, but cannot be completely avoided. Myocardial injury biomarkers (MIBs) can quickly and specifically reflect the degree of myocardial injury. Due to various reasons, there is no consensus on the specific values of MIBs in evaluating postoperative prognosis. This retrospective study was aimed to investigate the impact of MIBs on the mid-term prognosis of patients undergoing off-pump coronary artery bypass grafting (OPCABG). Methods Totally 564 patients undergoing OPCABG with normal courses were included. Cardiac troponin T (cTnT) and creatine kinase myocardial band (CK-MB) were assessed within 48 h before operation and at 6, 12, 24, 48, 72, 96 and 120 h after operation. Patients were grouped by peak values and peak time courses of MIBs. The profile of MIBs and clinical variables as well as their correlations with mid-term prognosis were analyzed by univariable and multivariable Cox regression models. Result Continuous assessment showed that MIBs increased first (12 h after surgery) and then decreased. The peak cTnT and peak CK-MB occurred within 24 h after operation in 76.8% and 67.7% of the patients respectively. No significant correlation was found between CK-MB and mid-term mortality. Delayed cTnT peak (peak cTnT elevated after 24 h after operation) was correlated with lower creatinine clearance rate (69.36 ± 21.67 vs. 82.18 ± 25.17 ml/min/1.73 m2), body mass index (24.35 ± 2.58 vs. 25.27 ± 3.26 kg/m2), less arterial grafts (1.24 ± 0.77 vs. 1.45 ± 0.86), higher EuroSCORE II (2.22 ± 1.12 vs.1.72 ± 0.91) and mid-term mortality (26.5 vs.7.9%). Age (HR: 1.067, CI: 1.006–1.133), left ventricular ejection fraction (HR: 0.950, CI: 0.910–0.993), New York Heart Association score (HR: 1.839, CI: 1.159–2.917), total venous grafting (HR: 2.833, CI: 1.054–7.614) and cTnT peak occurrence within 24 h (HR: 0.362, CI: 0.196–0.668) were independent predictors of mid-term mortality. Conclusion cTnT is a better indicator than CK-MB. The peak value and peak occurrence of cTnT are related to mid-term mortality in patients undergoing OPCABG, and the peak phases have stronger predictive ability. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000033850. Registered 14 June 2020, http://www.chictr.org.cn/edit.aspx?pid=55162&htm=4.


2019 ◽  
Vol 40 (26) ◽  
pp. 2155-2163 ◽  
Author(s):  
Filippos Triposkiadis ◽  
Javed Butler ◽  
Francois M Abboud ◽  
Paul W Armstrong ◽  
Stamatis Adamopoulos ◽  
...  

Abstract Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2158-2158
Author(s):  
Hala Mounir Mohamed Moustafa Agha ◽  
Antoine AbdelMassih ◽  
Mohamed Youssef Abd El Rahman ◽  
Ornella Milanesi, ◽  
Biagio Castaldi ◽  
...  

Abstract Background: Among patients with beta-thalassemia early detection of transfusion-induced myocardial iron loading and its intervention with aggressive chelation therapy may delay or reverse heart failure. Three dimensional speckle tracking echocardiography (3D-STE) is a novel tool that may early detect myocardial affection in these patients. Methods: Thirty-two thalassemic patients with a mean age of 18.1± 7.03 years and 30 aged matched healthy control subjects have been included in the study. Patients have been recruited from pediatric hematology clinics in both Cairo University, Egypt (n=18) and Padova University, Italy (n=14). 3D-STE was performed to all patients and control subjects in addition to the myocardial relaxometry T2* by cardiac MRI. Results: The left ventricular ejection fraction (LVEF) derived from 3D echocardiography among the studied thalassemia patients was within normal range 62.5± 5.6%. Compared to the normal subjects, thalassemia patients had a statistical significant reduction of the left ventricular global longitudinal strain (-16.81± 0.93% vs -18.76 ± 1.12 %, p=0.001), the left ventricular global circumferential strain (-10.56 ± 0.61% vs -11.83 ± 0.71 %, p=0.001 ) and the left ventricular global area strain (-20.13 ±1.18% vs -22.48 ±,1.29 %, p=0.001). No statistical significant correlation was found between the severity of myocardial iron overload measured by T2* and the measured left ventricular global strain. Conclusion: In asymptomatic thalassemia patients with preserved left ventricular global systolic function 3D-STE derived strain can detect early subtle myocardial dysfunction. The observed subtle myocardial deformation dysfunction is not related to the extent of myocardial iron deposition. Disclosures No relevant conflicts of interest to declare.


2016 ◽  
Vol 22 (2) ◽  
pp. 153-158 ◽  
Author(s):  
Erkan Gencer ◽  
Volkan Doğan ◽  
Müjgan Tek Öztürk ◽  
Aydın Nadir ◽  
Ahmet Musmul ◽  
...  

Background: Cardiac troponins (cTn) are reliable and the most sensitive biomarker in the setting of acute decompensated heart failure (ADHF). Acute decompensated heart failure is usually associated with worsening chronic heart failure, and it may be caused by ongoing minor myocardial cell damage that may occur without any reported precipitating factors. Methods: We compared the short-term effect of levosimendan (LEV), dobutamine (DOB), and vasodilator treatment (nitroglycerin [NTG]) on myocardial injury with hemodynamic, neurohumoral, and inflammatory indicators. One hundred twenty-two patients with a mean age of 66 ± 9 years were treated with LEV (n = 40), DOB (n = 42), and NTG (n = 40) and examined retrospectively. Blood samples (cTnI, N-terminal probrain natriuretic peptide [NT-proBNP], highly sensitive C-reactive protein [HsCRP], and others), left ventricular ejection fraction (LVEF), systolic pulmonary artery pressure (sPAP), and 6-minute walk distance (6MWD) were compared before and after treatment. Results: At admission, detectable levels of cTnI were observed in 53% of patients (≥0.05 ng/mL). Serial changes in the mean cTnI levels were not significantly different between the groups (LEV 0.04 ± 0.01 to 0.03 ± 0.01 ng/mL; DOB 0.145 ± 0.08 to 0.08 ± 0.03 ng/mL; NTG 0.1 ± 0.03 to 0.09 ± 0.02 ng/mL; overall P = .859). Favourable effects on the NT-proBNP, sPAP values, LVEF, 6MWD, and HsCRP were observed overall, especially in the LEV groups. Conclusion: Beneficial effects of short-term use of LEV, DOB, and NTG on ongoing myocardial injury were demonstrated. These findings can be attributed to the anti-ischemic properties as well as the hemodynamic, neurohumoral, and functional benefits from the positive inotropes, especially LEV, in patients with ADHF.


2020 ◽  
Vol 9 (8) ◽  
pp. 2524
Author(s):  
Rebeca Lorca ◽  
María Martín ◽  
Isaac Pascual ◽  
Aurora Astudillo ◽  
Beatriz Díaz Molina ◽  
...  

Left ventricle non-compaction cardiomyopathy (LVNC) has gained great interest in recent years, being one of the most controversial cardiomyopathies. There are several open debates, not only about its genetic heterogeneity, or about the possibility to be an acquired cardiomyopathy, but also about its possible overdiagnosis based on imaging techniques. In order to better understand this entity, we identified 38 LVNC patients diagnosed by cardiac MRI (CMRI) or anatomopathological study that could underwent NGS-sequencing and clinical study. Anatomopathological exam was performed in eight available LVNC hearts. The genetic yield was 34.2%. Patients with negative genetic testing had better left ventricular ejection fraction (LVEF) or it showed a tendency to improve in follow-up, and a possible trigger factor for LVNC was identified in 1/3 of them. Nonetheless, cerebrovascular accidents occurred in similar proportions in both groups. We conclude that in LVNC there seem to be different ways to achieve the same final phenotype. Genetic testing has a good genetic yield and provides valuable information. LVNC without an underlying genetic cause may have a better prognosis in terms of LVEF evolution. However, anticoagulation to prevent cerebrovascular accident (CVA) should be carefully evaluated in all patients. Larger series with pathologic examination are needed to help better understand this entity.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fausto Pizzino ◽  
Giampiero Vizzari ◽  
Rubina Qamar ◽  
Charles Bomzer ◽  
Scipione Carerj ◽  
...  

Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies.


Author(s):  
Ikutaro Nakajima ◽  
Ryohsuke Narui ◽  
Asad A. Aboud ◽  
Oluwaseun Adeola ◽  
Julia McHugh ◽  
...  

Background - Periaortic fibrotic ventricular tachycardia (VT) substrate is common in nonischemic cardiomyopathy (NICM), often intramural, and difficult to ablate. We sought to better characterize normal and abnormal periaortic voltage map parameters and NICM periaortic VTs. Methods - In 15 patients without heart disease, the 5 th percentile of endocardial voltage for increasing distance from the aortic valve ring was determined. In 53 consecutive NICM patients (64±11 years; left ventricular ejection fraction 31±10%) undergoing ablation of recurrent VT, periaortic electrogram voltage and VT characteristics were analyzed. Results - In healthy patients, the 5 th percentile of the bipolar voltage (BV) increased proportional to the distance from the aortic valve ring, from 1.0mV at 1cm to 1.5mV at 1.5cm; the corresponding unipolar voltage (UV) cutoffs were 5.0mV and 7.5mV. A total of 160 VTs were induced in 53 NICM patients, of which 28 VTs in 20 patients had periaortic origins. Periaortic VTs were associated with similar periaortic BV, but lower UVs consistent with intramural fibrosis as an important substrate. Periaortic VTs could be divided into left (LBBB) and right (RBBB) bundle branch block forms with mapping showing right septal and lateral exits. LBBB VTs were more often acutely abolished with ablation (100% vs. 69%; p=0.034), but with a 23% incidence of heart block. Greater extent of low voltage was associated with more induced VTs and worse acute outcome. Conclusions - Adjusting voltage parameters based on distance from the aortic valve may improve definition of LVOT arrhythmia substrate. Periaortic VTs are common in NICM, often associated with intramural substrate and can be divided into LBBB and RBBB types associated with different ablation outcomes and risks.


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