[Heart and cancer: cardio-oncology]. / Herz und Krebs: Kardioonkologie.

Cardiovascular diseases and cancer have a complex relationship and show a reciprocal linkage and influence. Mutual risk factors, demographic changes and increasing multimorbidity result in an increase in the incidence of both diseases. Advances in oncological and cardiological treatment lead to a further increase in patients with cured or chronic diseases as a relevant comorbidity. The induction of cardiovascular side effects by cancer therapies leads to increased cardiovascular morbidity and mortality in cancer patients. Recent data also show that cardiovascular disease, through various factors, can also promote the development and progression of cancer. An understanding of the interrelationship between cardiovascular diseases and cancer can be seen as a major medical challenge for the future. To this end, scientific, structural, clinical and educational interfaces between cardiology and oncology are essential. This article outlines the complex relationships between cardiovascular diseases and cancer and defines current and future challenges for the best possible care of affected patients.

[Update cardio-oncology : Immune checkpoint inhibitor therapy]. / Update Kardioonkologie : Immuncheckpoint-Inhibitor-Therapie.

Cardiovascular diseases and cancer are the most common causes of death in Germany. Cancer treatment can lead to significant cardiovascular side effects and thus form a link between the two disease groups. The focus of cardio-oncology is on the best possible prevention, diagnostics and treatment of cardiovascular complications caused by cancer treatment. It is crucial for cardio-oncology to adapt to the continuous development of new forms of oncological treatment with previously unknown cardiovascular side effects. One such new form of treatment is immune checkpoint inhibitor (ICI) therapy, which is regarded as the most important oncological milestone of the last decade due to its excellent oncological efficacy; however, the growing use has revealed a high risk of diverse cardiovascular side effects with high morbidity and mortality, so that cardio-oncological care of affected patients is of particular importance. This review summarizes the current scientific and clinical state of the pathophysiology, incidence, diagnosis and treatment of cardiovascular side effects of ICI therapy.

Cellular Alterations in Immune Checkpoint Inhibitor Therapy-Related Cardiac Dysfunction.

PURPOSE OF REVIEW: Immune checkpoint inhibitor (ICI) therapy has emerged as a pivotal advancement in cancer treatment, but the widespread adoption has given rise to a growing number of reports detailing significant cardiovascular toxicity. This review concentrates on elucidating the mechanisms behind ICI-related cardiovascular complications, emphasizing preclinical and mechanistic data. RECENT FINDINGS: Accumulating evidence indicates a more significant role of immune checkpoints in maintaining cardiac integrity than previously understood, and new key scientific data are available to improve our understanding of ICI-related cardiovascular toxicity, including hidden cardiotoxicity. New avenues for innovative concepts are hypothesized, and opportunities to leverage the knowledge from ICI-therapy for pioneering approaches in related scientific domains can be derived from the latest scientific projects. Cardiotoxicity from ICI therapy is a paramount challenge for cardio-oncology. Understanding the underlying effects builds the foundation for tailored cardioprotective approaches in the growing collective at risk for severe cardiovascular complications.

Current Therapies and Future Horizons in Cardiac Amyloidosis Treatment.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid. RECENT FINDINGS: The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy.

(Non)-Exertional Variables of Cardiopulmonary Exercise Testing in Heart Failure with and Without Cardiac Amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO2peak). RECENT FINDINGS: We retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO2 (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO2peak (p = 0.127). Higher performance was correlated with lower E/e' and NTproBNP as well as higher resting heart rate and stroke volume in CA. Patients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction.

[2022 ESC guidelines on cardio-oncology : Understanding and treating cardiovascular side effects from cancer therapy]. / ESC-Leitlinie 2022 onkologische Kardiologie : Kardiovaskuläre Nebenwirkungen durch Krebstherapie verstehen und behandeln.

The continuous improvement in cancer treatment leads to a growing number of long-term survivors. Arguably, the treatment of cardiovascular side effects from cancer therapy is therefore of major importance for the morbidity and mortality affected patients. The 2022 ESC guidelines on cardio-oncology of the European Society of Cardiology (ESC) aim to improve the treatment of affected patients across the entire continuum of therapy and in the long term by establishing standardized procedures for prevention, diagnostics, and treatment of cardiovascular side effects. Suitable diagnostic and therapeutic measures for specific substance classes are defined on the basis of fundamental recommendations for cardio-oncological care in individual therapy phases. Furthermore, the guidelines provide a comprehensive focus on individual risk assessment before the start of therapy as the basis for determining the type and intensity of cardio-oncological care in the further course. In addition, the risk assessment serves as a basis for the initiation of suitable preventive measures to avoid or minimize the development of cardiovascular side effects during therapy. The present article provides an overview of the most important innovations of the 2022 ESC guidelines on cardio-oncology with respect to general definitions and recommendations as well as a summary of the most important recommendations for some specific forms of therapy with relevance for cardio-oncology in the future.

Cardiotoxicity from chimeric antigen receptor-T cell therapy for advanced malignancies.

Chimeric antigen receptor (CAR)-T cell therapy is the next revolutionary advance in cancer therapy. By using ex vivo engineered T cells to specifically target antigens, a targeted immune reaction is induced. Chimeric antigen receptor-T cell therapy is approved for patients suffering from advanced and refractory B cell and plasma cell malignancies and is undergoing testing for various other haematologic and solid malignancies. In the process of triggering an anticancer immune reaction, a systemic inflammatory response can emerge as cytokine release syndrome (CRS). The severity of CRS is highly variable across patients, ranging from mild flu-like symptoms to fulminant hyperinflammatory states with excessive immune activation, associated multiorgan failure and high mortality risk. Cytokine release syndrome is also an important factor for adverse cardiovascular (CV) events. Sinus tachycardia and hypotension are the most common reflections, similar to what is seen with other systemic inflammatory response syndromes. Corrected QT interval prolongation and tachyarrhythmias, including ventricular arrhythmias and atrial fibrillation, also show a close link with CRS. Events of myocardial ischaemia and venous thromboembolism can be provoked during CAR-T cell therapy. Although not as closely related to CRS, changes in cardiac function can be observed to the point of heart failure and cardiogenic shock. This may also be encountered in patients with severe valvular heart disease in the setting of CRS. This review will discuss the pertinent CV risks of the growing field of CAR-T cell therapy for today's cardiologists, including incidence, characteristics, and treatment options, and will conclude with an integrated management algorithm.

Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy.

AIMS: Cardiac immune-related adverse events (irAEs) from immune checkpoint inhibition (ICI) targeting programmed death 1 (PD1) are of growing concern. Once cardiac irAEs become clinically manifest, fatality rates are high. Cardio-oncology aims to prevent detrimental effects before manifestation of severe complications by targeting early pathological changes. We therefore aimed to investigate early consequences of PD1 inhibition for cardiac integrity to prevent the development of overt cardiac disease. METHODS AND RESULTS: We investigated cardiac-specific consequences from anti-PD1 therapy in a combined biochemical and in vivo phenotyping approach. Mouse hearts showed broad expression of the ligand PDL1 on cardiac endothelial cells as a main mediator of immune-crosstalk. Using a novel melanoma mouse model, we assessed that anti-PD1 therapy promoted myocardial infiltration with CD4+ and CD8+ T cells, the latter being markedly activated. Left ventricular (LV) function was impaired during pharmacological stress, as shown by pressure-volume catheterization. This was associated with a dysregulated myocardial metabolism, including the proteome and the lipidome. Analogous to the experimental approach, in patients with metastatic melanoma (n = 7) receiving anti-PD1 therapy, LV function in response to stress was impaired under therapy. Finally, we identified that blockade of tumour necrosis factor alpha (TNFα) preserved LV function without attenuating the anti-cancer efficacy of anti-PD1 therapy. CONCLUSIONS: Anti-PD1 therapy induces a disruption of cardiac immune homeostasis leading to early impairment of myocardial functional integrity, with potential prognostic effects on the growing number of treated patients. Blockade of TNFα may serve as an approach to prevent the manifestation of ICI-related cardiotoxicity.

Anthracycline Therapy Modifies Immune Checkpoint Signaling in the Heart.

Cancer survival rates have increased significantly because of improvements in therapy regimes and novel immunomodulatory drugs. Recently, combination therapies of anthracyclines and immune checkpoint inhibitors (ICIs) have been proposed to maximize neoplastic cell removal. However, it has been speculated that a priori anthracycline exposure may prone the heart vulnerable to increased toxicity from subsequent ICI therapy, such as an anti-programmed cell death protein 1 (PD1) inhibitor. Here, we used a high-dose anthracycline mouse model to characterize the role of the PD1 immune checkpoint signaling pathway in cardiac tissue using flow cytometry and immunostaining. Anthracycline treatment led to decreased heart function, increased concentration of markers of cell death after six days and a change in heart cell population composition with fewer cardiomyocytes. At the same time point, the number of PD1 ligand (PDL1)-positive immune cells and endothelial cells in the heart decreased significantly. The results suggest that PD1/PDL1 signaling is affected after anthracycline treatment, which may contribute to an increased susceptibility to immune-related adverse events of subsequent anti-PD1/PDL1 cancer therapy.

PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction.

The programmed cell death protein 1 (PD1) immune checkpoint prevents inflammatory tissue damage by inhibiting immune reactions. Understanding the relevance of cardiac PD1 signaling may provide new insights into the inflammatory events under baseline conditions and disease. Here, we demonstrate distinct immunological changes upon PD1 deficiency in healthy hearts and during reperfused acute myocardial infarction (repAMI). In PD1-deficient mice, upregulated inflammatory cytokines were identified under baseline conditions including cardiac interleukins and extracellular signal-related kinase 1/2 (ERK1/2). A murine in vivo repAMI model to determine inflammatory changes in the early phase showed downregulation of the ligand PDL1, paralleled by an endothelial injury, indicated by loss of the CD31 signal. Immunofluorescence imaging showed decreased PDL1 expression specifically in the infarct zone, highlighting an involvement in PDL1 in myocardial injury response. Pharmacological depletion of PD1 prior to repAMI did not alter the area of infarction but led to increased numbers of CD8+ T cells in treated mice. We conclude that PD1/PDL1 signaling plays a significant role in healthy hearts and repAMI, emphasizing the relevance of adaptive immunity during myocardial injury. The findings highlight the risk for adverse outcomes from acute myocardial infarction in the growing group of patients receiving immune checkpoint inhibitor therapy.

Oncocardiology: new challenges, new opportunities.

Patients with cancer are at a higher risk of cardiovascular disease, which contributes to significant morbidity and mortality. The rapid progress in the field of oncological treatments has led to a steady increase in long-term cancer survivors. Care for cardiovascular complications is therefore becoming increasingly important. In addition, the establishment of new oncological therapies has resulted in the identification of previously unknown cardiovascular side effects. Oncocardiology aims to detect and treat cardiovascular diseases associated with cancer and cancer therapy. Continuous scientific, clinical, and structural developments are necessary as the basis for the best care of the growing number of affected patients. This review summarizes current developments in the field of oncocardiology with regard to advances in cancer therapy and challenges in clinical oncocardiology work. Cardiovascular side effects by targeted cancer therapies are characterized and recent advances in the field of cardiovascular diagnostics are outlined. Developments to better integrate oncocardiology into the medical care system and perspectives for modern, patient-oriented care are shown. In light of the coronavirus disease 2019 (COVID-19) pandemic, current challenges and opportunities are highlighted. The relevance of profitable further advances in oncocardiology including standardized guidelines and educational programs is delineated as a mandatory requirement for the successful development of oncocardiology.

Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system.

Immune checkpoint inhibitor (ICI) therapy induces an immune response against cancer cells. Immune checkpoint inhibitor therapy has tremendously improved the prognosis for a large number of cancers, but is associated with considerable immune-related adverse events (irAEs). Cardiovascular complications from ICI therapy occur in a modest proportion of patients, but show the highest lethality rates of all ICI-related complications. While ICI-related myocarditis is the most dangerous complication, its clinical manifestation varies, e.g., asymptomatic reduction of left ventricular function, isolated increase in cardiac troponins, and arrhythmias. This review delineates current data on cardiovascular complications of ICI therapy. The effects of ICI therapy on the cardiovascular system are classified in the context of preclinical data on the biochemical and immunological function of the immune checkpoint signaling pathways in the heart and the vascular system. Incidence, suspected pathomechanisms, typical symptoms, as well as recommended diagnostics are summarized. Current therapy recommendations for ICI-related cardiotoxicity are outlined and innovative new approaches with high potential for improving outcome in ICI-related myocarditis are delineated. A better understanding of cardiovascular complications is essential for the best possible oncocardiology care of the growing number of patients undergoing ICI therapy.

High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy.

BACKGROUND: Cancer therapy-related cardiovascular toxicity (CTR-CVT) from immune checkpoint inhibitor (ICI) therapy is still incompletely characterized, and patients with pre-existing cardiovascular disease represent a particularly high-risk cohort. Valid parameters for risk stratification of these patients are missing. Neutrophil-to-lymphocyte ratio (NLR) has been shown to predict mortality and adverse events in other cardiovascular cohorts. The present study aims to examine the predictive capacity of NLR for risk stratification of patients particularly vulnerable for CTR-CVT under ICI therapy. METHODS: We performed an analysis of 88 cancer patients (69 ± 11 years, 25% female) with pre-existing cardiovascular disease under ICI therapy from the prospective Essen Cardio-Oncology Registry (ECoR). NLR was assessed at patient enrollment and the population was divided through receiver operator characteristic (ROC) curve analysis in patients with low (< 4.57) and high (≥ 4.57) NLR. Endpoint was the whole spectrum of CTR-CVT, according to the European guidelines on cardio-oncology. The median follow-up was 357 days (interquartile range (IQR): 150-509 days). RESULTS: We observed 4 cases of myocarditis, 17 cases of vascular toxicity, 3 cases of arterial hypertension, 22 cases of arrhythmia or QTc prolongation and 17 cases of cardiovascular dysfunction. NLR was associated with overall CTR-CVT by univariable Cox regression (hazard ratio (HR): 1.443; 95% confidence interval (CI) 1.082-1.925; p = 0.013). However, this association was attenuated after adjusting for further confounders. CONCLUSION: NLR is moderately associated with CTR-CVT in cancer patients with pre-existing cardiovascular disease under ICI therapy. Surveillance of NLR during ICI therapy might be an effective and economically biomarker for risk stratification in these high-risk patients.

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography.

Background: Cardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. Methods: The study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. Results: Detectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45-1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39-1.90) for the first tertile to 2.02 (95 % CI 1.74-2.35) for the third tertile. Conclusions: Detectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Frequency and prognosis of CVD and myocardial injury in patients presenting with suspected COVID-19 - The CoV-COR registry.

Background: The COVID-19 pandemic led to an alteration of algorithms in emergency medicine, which may influence the management of patients with similar symptoms but underlying cardiovascular diseases. We evaluated key differential diagnoses to acute COVID-19 infection and the prevalence and the prognosis of myocardial injury in patients presenting for suspected COIVD-19 infection. Methods: This prospective observational study includes patients presenting with symptoms suggestive of COVID-19 infection during the pandemic. In patients without COVID-19, leading diagnoses was classified according to ICD-10. Myocardial injury was defined as elevated high-sensitivity Troponin I with at least one value above the 99th percentile upper reference limit and its prevalence together with 90-days mortality rate was compared in patients with vs without COVID-infection. Results: From 497 included patients (age 62.9 ± 17.2 years, 56 % male), 314 (63 %) were tested positive on COVID-19 based on PCR-testing, while another cause of symptom was detected in 183 patients (37 %). Cardiovascular diseases were the most frequent differential diagnoses (40 % of patients without COVID-19), followed by bacterial infection (24 %) and malignancies (16 %). Myocardial injury was present in 91 patients (COVID-19 positive: n = 34, COVID-19 negative: n = 57). 90-day mortality rate was higher in patients with myocardial injury (13.4 vs 4.6 %, p = 0.009). Conclusion: Cardiovascular diseases represent the most frequent differential diagnoses in patients presenting to a tertiary care emergency department with symptoms suggestive of an acute infection. Screening for cardiovascular disease is crucial in the initial evaluation of symptomatic patients during the COVID pandemic to identify patients at increased risk.Trial Registration:Clinicaltrials.gov Identifier: NCT04327479.

[Drug-induced cardiomyopathies]. / Medikamentös bedingte Kardiomyopathien.

Drug-induced cardiovascular side effects have a significant impact on morbidity and mortality. The demographic change and improved long-term survival particularly in cancer patients have caused an increasing number of affected patients, hence emphasizing the importance of the best possible treatment of such complications. This article gives an overview of classic and modern groups of substances with cardiotoxic effects and summarizes the principles of diagnostics and therapy. After characterizing the common cardiovascular side effects caused by anthracycline chemotherapy, we focus on complications caused by modern forms of immunotherapy, considering its significant impact on oncological therapy in the future due to its growing clinical application. In addition to specific cancer therapies, accompanying measures such as blood transfusions in patients with hematologic diseases can also lead to severe cardiovascular complications. In the last section, we classify important features and therapeutic approaches in cardiac involvement of transfusion-related hemochromatosis. A good knowledge of the characteristics of specific cardiovascular side effects can help to improve the management of affected patients.

Right ventricular and atrial strain in patients with advanced melanoma undergoing immune checkpoint inhibitor therapy.

AIMS: While immune checkpoint inhibitor (ICI) therapy significantly improves survival rates in advanced melanoma, ICI can evoke severe immune-related cardiovascular adverse events. Right ventricular (RV) dysfunction negatively impacts the outcomes in cardiovascular diseases and may be an early sign for overall cardiotoxicity. We aimed to assess RV function in melanoma patients undergoing ICI therapy using conventional echocardiographic and strain imaging techniques. METHODS AND RESULTS: We retrospectively examined 30 patients (40% women, age 59 ± 13 years) with advanced melanoma (stage III/IV) before and 4 weeks after the start of ICI therapy (follow-up at 39 ± 15 days); n = 15 of the patients received nivolumab, and n = 15 received the combination therapy nivolumab/ipilimumab. Two-dimensional echocardiography with assessment of RV longitudinal strain of the free wall (RV-LSFW) and assessment of right atrial (RA) strain from speckle tracking was performed at baseline and after the start of ICI therapy. Short-term ICI therapy caused a reduction of RV-LSFW (-25.5 ± 6.4% vs. -22.4 ± 4.3%, P = 0.002) and of RA strain during contraction phase (-10.6 ± 3.5% vs. -7.7 ± 3.1%, P = 0.001). Conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and pulmonary artery systolic pressure were not different between the two time points (TAPSE 26 ± 5 vs. 25 ± 5 mm, P = 0.125; FAC 38 ± 13% vs. 38 ± 14%, P = 0.750; and pulmonary artery systolic pressure 27 ± 10 vs. 25 ± 8 mmHg, P = 0.268). CONCLUSIONS: Analysis of RV and RA strain shows alterations even in a short-term follow-up, while changes in RV function are not visible by conventional RV parameters. Alterations in RV and RA strain could be early signs of cardiotoxicity and therefore should be assessed in patients undergoing ICI therapy.

Assessment of coronary artery disease during hospitalization for cancer treatment.

BACKGROUND: With improvement of cancer-specific survival, comorbidities and treatment-related side effects, particularly cardiovascular toxicities, need close attention. The aim of the present study was to evaluate clinical characteristics and outcomes of cancer patients requiring coronary angiography during inpatient care. METHODS: We performed a retrospective analysis of patients hospitalized between 02/2011 and 02/2018 in our two university hospital cancer centers. From a cohort of 60,676 cancer patients, we identified 153 patients (65.7 ± 11.6 years, 73.2% male), who underwent coronary angiography and were eligible for analysis. These were compared to a control group of 153 non-cancer patients pair-matched with respect to age, sex, and indication for catheterization. RESULTS: Cancer patients presented in 66% with an acute coronary syndrome (ACS). The most prevalent cancer entities were lymphoma (19%) and lung cancer (18.3%). The rate of primary percutaneous coronary interventions (PCI) was significantly lower in the cancer cohort (40.5% vs. 53.6%, p = 0.029), although manifestation of coronary artery disease (CAD) and PCI results were comparable (SYNergy between PCI with TAXus and cardiac surgery (SYNTAX)-score, delta pre- and post-PCI - 9.8 vs. - 8.0, p = 0.2). Mortality was remarkably high in cancer patients (1-year mortality 46% vs. 8% in non-cancer patients, p < 0.001), particularly with troponin-positive ACS (5-year mortality 71%). CONCLUSION: Strategies to effectively control cardiovascular risks in cancer patients are needed. Additionally, suspected CAD in cancer patients should not prevent prompt diagnostic clarification and optimal revascularization as PCI results in cancer patients are comparable to non-cancer patients and occurrence of troponin-positive ACS leads to a significantly increased risk of mortality.

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

AIMS: Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. METHODS AND RESULTS: PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). CONCLUSIONS: BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.