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.

Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular endothelial growth factor activity improves survival of cancer patients. Cardiovascular complications are critical and it is unknown whether these require specific treatment strategies. We aimed to clarify the associated risk of cardiovascular adverse events in patients treated with tyrosine kinase inhibitors. Design The design of this study was a meta-analysis of randomised controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of Science databases for randomised controlled trials published until January 2017 that assessed patients with different types of cancer treated with or without tyrosine kinase inhibitors in addition to standard chemotherapy. Results A total of 29,252 patients from 71 randomised controlled trials were included. Tyrosine kinase inhibitor treatment was associated with a higher cardiac ischaemia relative risk (relative risk = 1.69; 95% confidence interval: 1.12-2.57; p = 0.01), with the highest risks observed for sorafenib and patients with renal cancer. Risk of thrombocytopaenia (relative risk = 2.2; 95% confidence interval: 1.73-2.79; p < 0.001) was highest for regorafenib and patients with breast cancer. Left ventricular systolic dysfunction was increased after tyrosine kinase inhibitor therapy (relative risk = 2.53; 95% confidence interval:1.79 - 3.57; p < 0.001), with the highest risks reported for sunitinib and hepatocellular cancer. QT corrected interval prolongation (relative risk = 6.25; 95% confidence interval: 3.44-11.38; p < 0.001) and arterial hypertension (relative risk = 3.78; 95% confidence interval: 3.15-4.54; p < 0.001) were reported. The relative risks of arterial adverse events, cerebral ischaemia, venous adverse events and pulmonary embolism were similar across groups. Conclusion Tyrosine kinase inhibitors increase the risk of severe cardiovascular and particularly thrombotic adverse events. Specific treatment regimens when prescribing tyrosine kinase inhibitor therapies appear desirable.

Risk assessment in patients with acute coronary syndromes (ACS) is critical in order to provide adequate treatment. We performed a systematic meta-analysis to assess the predictive role of serum C-reactive protein (CRP) in patients with ST-segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention (PPCI). We included 7 studies, out of 1,033 studies, with a total of 6,993 patients with STEMI undergoing PPCI, which were divided in the high or low CRP group, according to the validated cut-off values provided by the corresponding CRP assay. High CRP values were associated with increased in-hospital and follow-up all-cause mortality, in-hospital and follow-up major adverse cardiac events (MACE), and recurrent myocardial infarction (MI). The pre-procedural CRP predicted in-hospital target vessel revascularization (TVR), but was not associated with acute/subacute and follow-up in-stent restenosis (ISR), and follow-up TVR. Thus, pre-procedural serum CRP could be a valuable predictor of global cardiovascular risk, rather than a predictor of stent-related complications in patients with STEMI undergoing PPCI. This biomarker might have the potential to improve the management of these high-risk patients.

Aims Unsuccessful weaning from ventilator after major cardiovascular procedures has been shown to be associated with increased post‐operative morbidity and mortality. Our study aimed to identify predictors and clinical implications of prolonged mechanical ventilation (PMV) after left ventricular assist device (LVAD) implantation. Methods and results We analysed the data of patients receiving a continuous‐flow LVAD in our centre from December 2010 to September 2017. PMV was defined by a duration of invasive ventilation of >7 days after LVAD implantation. Multivariable logistic regression analysis was performed for predictors of PMV. Survival was estimated by the Kaplan–Meier method. During the study period, 156 patients received a continuous‐flow LVAD in our centre. Seventeen patients were excluded due to early death (<7 days), and 139 patients were enrolled in the study (mean age: 58 years; male: 84%). The median duration of mechanical ventilation post‐operatively was 94 h (range: 5 to 4192 h). PMV was observed in 43% of patients. Patients on PMV were characterized by a more severe disease state at baseline, compared with the group of early extubation, as reflected by their Interagency Registry for Mechanically Assisted Circulatory Support level (Level 1–3: 72 vs. 49%, P = 0.008). Patients on PMV exhibited higher pulmonary wedge pressures (25 vs. 21 mmHg, P = 0.04), lower estimated glomerular filtration rate (53 vs. 60 mL/min/1.73 m 2 , P = 0.02), lower haemoglobin (10.6 vs. 11.6 g/dL, P = 0.02), and lower platelet counts (189 vs. 240/nL, P = 0.02). Previous sternotomy was more frequent in the PMV group (32 vs. 13%, P = 0.006). Higher rates of preoperative circulatory support (30 vs. 11.4%, P = 0.006), dialysis (31.7 vs. 10.1%, P = 0.001), and invasive ventilation (35 vs. 7.6%, P < 0.001) were reported for the PMV group. Logistic regression analysis revealed that estimated glomerular filtration rate [odds ratio (OR) 0.977, confidence interval (CI) 0.955–0.999, P = 0.038], platelet count (OR 0.994, CI 0.989–0.998, P = 0.008), and previous sternotomy (OR 5.079, CI 1.672–15.427, P = 0.004) were independent predictors of PMV. PMV was accompanied by longer intensive care unit (24 vs. 4 days, P < 0.001) and hospital stay (47 vs. 32 days, P = 0.003). Survival analysis revealed a profound increase in mortality at 180‐day post‐implantation in the PMV group (62 vs. 10%, log‐rank: P < 0.001). Conclusions Prolonged mechanical ventilation affects nearly half of patients after LVAD implantation. Previous ste...

Background: Parameters that mark the timing of left ventricular (LV) reverse remodeling following transcatheter aortic valve replacement (TAVR) are incompletely defined. This study aims to identify the dynamics of LV strain derived from speckle tracking echocardiography in a cohort of patients with severe aortic stenosis (AS) who underwent TAVR and its correlation with postprocedural outcomes. Methods: We selected 150 consecutive patients (82 ± 4 years old, STS score 6.4 ± 6.2) who underwent transfemoral TAVR between 07/2016 and 12/2017 at our tertiary care center. All patients were evaluated at baseline, 1 week after TAVR, and 3 months following TAVR. Results: The global longitudinal strain (GLS) 1 week following TAVR was comparable to that at baseline (− 15,9 ± 4.3 vs − 16.8 ± 4.1; p = NS) but significantly improved at 3 months following TAVR (− 15.9 ± 4.3% vs.-19.5 ± 3.5%; p < 0.001). No significant changes in global circumferential strain (GCS) and global radial strain (GRS) were detectable. The ejection fraction was significantly improved 1 week after the TAVR procedure. The baseline GLS correlated directly with the complication rate (R = 0.36, p = 0.005). The linear regression analysis showed that the main predictors of the improvement in the GLS at 3 months in our cohort were baseline GRS and GCS. Conclusion: GLS improves at 3 months after TAVR, while LV ejection fraction does not show a substantial change, signaling an early recovery of LV longitudinal function after the intervention. Additionally, GLS has a direct correlation with the postprocedural outcomes. GLS improvement might emerge as a valuable parameter for a tailored follow-up in TAVR patients.

Background: The long-term survival of cancer patients has significantly improved over the past years. Despite their therapeutic efficacy, various cancer therapies are associated with cardiotoxicity. Therefore, timely detection of cardiotoxic adverse events is crucial. However, the clinical assessment of myocardial damage caused by cancer therapy remains difficult.Methods: This retrospective study was performed to evaluate the diagnostic value of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for monitoring cancer therapy-induced cardiomyopathy. A total of 485 cancer patients referred to our cardio-oncology unit between July 2018 and January 2020 were selected from our Essen Cardio-oncology Registry (ECoR). We included patients with all types of cancer. Plasma concentrations of cTnI and NT-proBNP were measured by radioimmunoassay, and two-dimensional left ventricular ejection fraction (2D-LVEF), diastolic function, and global longitudinal strain (GLS) were measured by transthoracic echocardiography. In 116 patients, assessment was conducted before the induction of cancer therapy and during a short-term follow-up period; n = 42 of these were treated for malignant melanoma, and n = 42 with serial measurements were under treatment for breast cancer.Results: In cross-sectional data, elevated NT-proBNP was associated with reduced LVEF and pathological GLS in the total cohort. A total of 116 patients had serial LVEF and biomarker measurements, and changes in NT-proBNP and troponin correlated with changes in LVEF during follow-up investigations. Similar to the total cohort, a subgroup of patients treated for malignant melanoma showed a correlation between the change in cTnI and the change in LVEF. In a subgroup analysis of patients undergoing breast cancer therapy, a correlation between the change in NT-proBNP and the change in LVEF could be detected. Thirty patients presented with chemotherapy-induced cardiomyopathy, defined as a significant LVEF decrease (> 10%) to a value below 50%. The number of patients with increased cTnI and NT-proBNP was significantly higher in patients with

BackgroundRed blood cell transfusion remains controversial in patients with acute coronary syndromes and particularly in patients with ST-elevation myocardial infarction (STEMI).MethodsWe systematically searched PubMed, Cochrane, EMBASE, and Web of Science for studies published until January 2017 describing the outcomes in patients with STEMI who received red blood cell transfusion, compared with patients who did not.ResultsA total of 21,770 patients with STEMI from 5 cohort studies were included in the meta-analysis, 984 (4.5%) received red blood cell transfusion and 20,786 (95.4%) did not. Red blood cell transfusion was associated with a higher risk of in-hospital and long-term mortality, emergency repeated percutaneous coronary intervention (PCI), reinfarction rate, stroke rate, and heart failure. The group with red blood cell transfusion had a slightly higher incidence of diabetes mellitus and hypertension, but a lower incidence of smoking. The two groups had the same incidence of prior myocardial infarction, prior coronary artery bypass graft surgery and malignancy. Prior heart failure, prior stroke and prior PCI were more frequent in the group that had received red blood cell transfusion. The mean nadir haemoglobin was 8.5 ± 0.1 g/dl in the group with red blood cell transfusion and 12.5 ± 0.4 g/dl in the control group, p < 0.001.ConclusionsRed blood cell transfusion increases the morbidity and mortality in patients with STEMI. This difference could not be explained by the higher morbidity in the red blood cell transfusion group alone. Further randomised controlled trials are required to provide a reliable haemoglobin threshold for these patients.Electronic supplementary materialThe online version of this article (10.1007/s12471-018-1137-x) contains supplementary material, which is available to authorized users.

We aimed to evaluate whether therapy with immune checkpoint inhibitors (ICI) leads to changes in electrocardiogram (ECG) parameters in melanoma patients. We retrospectively examined 41 patients (46% women, age 61 ± 12years) with advanced melanoma (stage III/IV) before and during ICI treatment from our “Essen Cardio-oncology Registry” (ECoR). ECGs were analyzed before and 4–12 weeks after therapy started (follow-up, 90 ± 51 days). Heart rate, PR time, QRS duration and duration of the corrected QT (QTc) interval were recorded. QT dispersion (QTd) was calculated. Heart rate, PR time, QRS and QTc did not differ when comparing values before and after therapy started. QTd was prolonged after therapy started (32 ± 16 ms vs. 47 ± 19 ms, n = 41, p < 0.0001). Subgroup analyses revealed prolonged QTd in patients that received a combination immunotherapy with ipilimumab and nivolumab (31 ± 14 ms vs. 50 ± 14 ms, n = 21, p < 0.0001), while QTd in patients with anti–programmed death 1 (PD-1) inhibitor monotherapy did not change after therapy started. QTd is prolonged in patients under ICI combination therapy, potentially signaling an increased susceptibility to ventricular arrhythmias.