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Background and aims: Cardiotoxicity from immune checkpoint inhibitor (ICI) therapy is a challenge in clinical practice, and the assessment of ICI-related myocarditis (ICI-M) is often complicated by a variable phenotype. Cardiac magnetic resonance imaging (CMR) is used frequently, but evidence is poor. Here, we aim to assess the role of CMR in the assessment of suspected ICI-M in a real-world clinical setting. Methods: All patients receiving CMR at our centre for suspected ICI-M between September 2019 and January 2024 were included and retrospectively analysed. CMR parameters were correlated with clinical, laboratory and echocardiographic parameters and stratified for presence of myocarditis as per final diagnosis. Results: A total of 55 patients who received CMR for suspected ICI-M were analysed, including 25 patients with ICI-M and 30 patients with non-myocarditis cardiotoxicity (non-M). The mean age (ICI-M versus (vs.) non-M) was 65.7 ± 13.6 vs. 67.3 ± 9.9 (p = 0.61) years, 32.0 % vs. 26.7 % (p = 0.67) were female, and 40.0 % vs. 26.7 % (p = 0.29) had pre-existing coronary heart disease. Cardiac biomarkers and echocardiographic data did not differ between the groups. In CMR analysis, presence of LGE was associated with ICI-M (56.0 % in ICI-M vs. 26.7 % in non-M, p = 0.03). Myocardial oedema was generally rare and not associated with ICI-M. Conclusion: In this real-life assessment of routine clinical practice, the diagnostic assessment of ICI-M is challenged by low sensitivity of common diagnostic measures, often requiring a multimodal approach. Presence of LGE in CMR is associated with ICI-M, but sensitivity and specificity are low. Prospective data to improve diagnostic criteria is needed.

Background: Smoking has conflicting results on outcomes following acute myocardial infarction (AMI). We evaluated the independent influence of smoking status on patient outcomes. Methods: We included patients with AMI undergoing invasive coronary angiography with available self-reported smoking status. The incidence of death of any cause was evaluated during a median follow-up of 1.14 years (range 0.36–3.40 years). Association between smoking status and long-term mortality was evaluated using multivariable adjusted Cox regression analysis. Results: From 1612 AMI patients (aged 65.7 ± 13.3 years, 72.1 % male), 378 patients (23.4 %) were current-smokers, 311 (19.3 %) ex-smokers, and 923 (57.3 %) non-smokers. Compared with non-smokers, current-smokers were younger (68.5 ± 13.0 vs. 58.6 ± 12.5, p

Objectives We evaluated the ability of the assessment of regional wall motion abnormalities (RWMA) detected via transthoracic echocardiography to predict the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department.Design Prospective single-centre observational study.Setting Tertiary care university hospital emergency unit.Participants Patients presenting to the emergency department with acute chest pain suggestive of obstructive CAD.Primary outcome measure The primary endpoint was defined as the presence of obstructive CAD, requiring revascularisation therapy.Results Overall, 657 patients (age 58.1±18.0 years, 53% men) were included in our study. RWMA were detected in 76 patients (11.6%). RWMA were significantly more frequent in patients reaching the primary endpoint (26.2% vs 7.6%, p

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

Abstract Background Maintaining the ability to perform self‐care is a critical goal in patients with cancer. We assessed whether the patient‐reported ability to walk 4 m and wash oneself predict survival in patients with pre‐terminal cancer. Methods We performed a prospective observational study on 169 consecutive hospitalized patients with cancer (52% female, 64 ± 12 years) and an estimated 1–12 months prognosis at an academic, inpatient palliative care unit. Patients answered functional questions for ‘today’, ‘last week’, and ‘last month’, performed patient‐reported outcomes (PROs), and physical function assessments. Results Ninety‐two (54%) patients reported the ability to independently walk 4 m and 100 (59%) to wash ‘today’. The median number of days patients reported the ability to walk 4 m and wash were 6 (IQR 0–7) and 7 (0–7) days (‘last week’); and 27 (5–30) and 26 (10–30) days (‘last month’). In the last week, 32% of patients were unable to walk 4 m on every day and 10% could walk on 1–3 days; 30% were unable to wash on every day and 10% could wash on 1–3 days. In the last months, 14% of patients were unable to walk 4 m on every day and 10% could only walk on 1–10 days; 12% were unable to wash on every day and 11% could wash on 1–10 days. In patients who could walk ‘today’ average 4 m gait speed was 0.78 ± 0.28 m/s. Patients who reported impaired walking and washing experienced more symptoms (dyspnoea, exertion, and oedema) and decreased physical function (higher Eastern Cooperative Oncology Group Performance Status, and lower Karnofsky Performance Status and hand‐grip strength [unable vs. able to walk ‘today’: 205 ± 87 vs. 252 ± 78 Newton, P = 0.001; unable vs. able to wash ‘today’: 204 ± 86 vs. 250 ± 80 Newton, P = 0.001]). During the 27 months of observation, 152 (90%) patients died (median survival 46 days). In multivariable Cox proportional hazards regression analyses, all tested parameters were independent predictors of survival: walking 4 m ‘today’ (HR 0.63, P = 0.015), ‘last week’ (per 1 day: HR 0.93, P = 0.011), ‘last month’ (per 1 day: HR 0.98, P = 0.012), 4 m gait speed (per 1 m/s: HR 0.45, P = 0.002), and washing ‘today’ (HR 0.67, P = 0.024), ‘last week (per 1 day HR 0.94, p=0.019), and ‘last month’ (per 1 day HR 0.99, P = 0.040). Patients unable to walk and wash experienced the shortest survival and most reduced functional status. Conclusions In patients with pre‐terminal cancer, the self‐reported ability to walk 4 m and wash were independent predictors of survival and associated with decreased functional status.

Abstract Background Hand grip strength (HGS) is a widely used functional test for the assessment of strength and functional status in patients with cancer, in particular with cancer cachexia. The aim was to prospectively evaluate the prognostic value of HGS in patients with mostly advanced cancer with and without cachexia and to establish reference values for a European‐based population. Methods In this prospective study, 333 patients with cancer (85% stage III/IV) and 65 healthy controls of similar age and sex were enrolled. None of the study participants had significant cardiovascular disease or active infection at baseline. Repetitive HGS assessment was performed using a hand dynamometer to measure the maximal HGS (kilograms). Presence of cancer cachexia was defined when patients had ≥5% weight loss within 6 months or when body mass index was

CD47 is a cell surface protein controlling phagocytotic activity of innate immune cells. CD47 blockade was investigated as an immune checkpoint therapy in cancer treatment, enhancing phagocytosis of tumor cells by macrophages. Anti-CD47 treatment also reduced injury size during reperfused acute myocardial infarction (repAMI) by enhancing phagocytotic acitivity of macrophages. Little is known about the impact of CD47 blockade on neutrophils, representing the main portion of early infiltrating immune cells after repAMI. Therefore, we performed 45 min of cardiac ischemia followed by 24 h of reperfusion, observing a decreased cardiac injury size measured by triphenyl tetrazolium chloride (TTC) Evan’s blue staining. We were able to detect this effect with an innovative three-dimensional method based on light sheet fluorescence microscopy (LSFM). This further allowed us a simultaneous analysis of neutrophil infiltration, showing an unaltered amount of injury-associated neutrophils with reduced cardiac injury volume from repAMI. This observation suggests modulated phagocytosis of cell debris by neutrophils. Therefore, we performed flow cytometry analysis, revealing an increased phagocytotic activity of neutrophils in vitro. These findings highlight that CD47 blockade also enhances phagocytosis of cardiac cell debris by neutrophils, which might be an additional protective effect of anti-CD47 treatment after repAMI.

Abstract Aims The initial and dynamic levels of B‐type natriuretic peptide (BNP) and N‐terminal‐prohormone BNP (NT‐proBNP) are routinely used in clinical practice to identify patients with acute and chronic heart failure. In addition, BNP/NT‐proBNP levels might be useful for risk stratification in patients with and without heart failure. We performed a meta‐analysis to investigate, whether the value of BNP/NT‐proBNP as predictors of long‐term prognosis differentiates in cohorts with and without heart failure. Methods and results We systematically searched established scientific databases for studies evaluating the prognostic value of BNP or NT‐proBNP. Random effect models were constructed. Data from 66 studies with overall 83 846 patients (38 studies with 46 099 patients with heart failure and 28 studies with 37 747 patients without heart failure) were included. In the analysis of the log‐transformed BNP/NT‐proBNP levels, an increase in natriuretic peptides by one standard deviation was associated with a 1.7‐fold higher MACE rate (hazard ratio [95% confidence interval]: 1.74[1.58–1.91], P

Abstract 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.

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.

Background and aims: Available data suggest that the use of IVUS for guidance of percutaneous coronary interventions (PCIs) improves the prognosis of patients undergoing complex interventions. We aimed to examine how the utilization of intravascular ultrasound (IVUS) affects patient survival irrespective of procedure complexity. Methods: The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography between 2004 and 2019. The incidence of death due to any cause was evaluated during a mean follow-up of 3.4 years. Cox regression analysis was used to determine the association of IVUS utilization with incident mortality. Results: Overall, data from 30,814 coronary angiography exams (mean age 64.9 ± 12.5 years, 70.3% male) were included, among which 4991 procedures (16.2%) were guided by IVUS. Utilization of IVUS was associated with a 35% reduction in mortality, independent of traditional risk factors (0.64(0.58–0.71), p

Objectives: To determine whether relevant comorbidities stratify patients with and without IE and whether these may improve the diagnostic accuracy, in addition to the modified Duke criteria. Methods and Results: 261 consecutive patients (aged 60.1 ± 16.1 years, 62.8% male) with suspected IE were prospectively included in this single-center observational trial. Modified Duke criteria and relevant comorbidities as well as clinical characteristics, were assessed. Forty-seven patients had IE, as confirmed by a clinical event committee. Patients with IE had a higher frequency of positive blood cultures (70.2% vs. 36.9%, p < 0.0001), embolic diseases (36.2% vs. 10.8%, p < 0.0001), heart murmurs (27.7% vs. 11.7%, p = 0.01), and intensive care therapy (74.5% vs. 58.4%, p = 0.04). In receiver operating characteristics, the combination of modified Duke criteria without transesophageal echocardiography led to an area under the curve of 0.783 (0.715–0.851). The predictive value was only marginally improved by the addition of heart murmur and intensive care therapy (0.794 [0.724–0.863]). In contrast, transesophageal echocardiography alone achieved an area under the curve of 0.956 (0.937–0.977) and was further improved when adding modified Duke criteria, heart murmur, and intensive care therapy (0.999 [0.998–1.000]). Conclusion: Modified Duke criteria provide excellent diagnostic value for evaluating suspected IE, mainly driven by transesophageal echocardiography. Trial registration: NCT03365193.

Abstract Coronavirus disease 2019 (COVID‐19) is challenging the care for cardiovascular patients, resulting in serious consequences with increasing mortality in pre‐diseased heart failure patients. In the current state of the pandemic, the physiopathology of COVID‐19 affecting pre‐diseased hearts and the management of terminal heart failure in COVID‐19 patients remain unclear. We outline the findings of a young COVID‐19 patient suffering from idiopathic cardiomyopathy who was treated for acute multi‐organ failure and required cardiac surgery with implantation of a temporary right ventricular and durable left ventricular assist device (LVAD). For deeper translational insights, we used in‐depth tissue analysis by electron and light sheet fluorescence microscopy revealing evidence for spatial distribution of severe acute respiratory syndrome coronavirus 2 in the heart. This indicates that in‐depth analysis may represent a valuable tool in understanding indistinct clinical cases. We conclude that COVID‐19 directly affects pre‐diseased hearts, but the consequences can be treated successfully with LVAD implantation.

Abstract 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

Abstract 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

The cardiac bioavailability of peptide drugs that inhibit harmful intracellular protein–protein interactions in cardiovascular diseases remains a challenging task in drug development. This study investigates whether a non-specific cell-targeted peptide drug is available in a timely manner at its intended biological destination, the heart, using a combined stepwise nuclear molecular imaging approach. An octapeptide (heart8P) was covalently coupled with the trans-activator of transcription (TAT) protein transduction domain residues 48–59 of human immunodeficiency virus-1 (TAT-heart8P) for efficient internalization into mammalian cells. The pharmacokinetics of TAT-heart8P were evaluated in dogs and rats. The cellular internalization of TAT-heart8P-Cy(5.5) was examined on cardiomyocytes. The real-time cardiac delivery of 68Ga-NODAGA-TAT-heart8P was tested in mice under physiological and pathological conditions. Pharmacokinetic studies of TAT-heart8P in dogs and rats revealed a fast blood clearance, high tissue distribution, and high extraction by the liver. TAT-heart-8P-Cy(5.5) was rapidly internalized in mouse and human cardiomyocytes. Correspondingly, organ uptake of hydrophilic 68Ga-NODAGA-TAT-heart8P occurred rapidly after injection with an initial cardiac bioavailability already 10 min post-injection. The saturable cardiac uptake was revailed by the pre-injection of the unlabeled compound. The cardiac uptake of 68Ga-NODAGA-TAT-heart8P did not change in a model of cell membrane toxicity. This study provides a sequential stepwise workflow to evaluate the cardiac delivery of a hydrophilic, non-specific cell-targeting peptide. 68Ga-NODAGA-TAT-heart8P showed rapid accumulation in the target tissue early after injection. The implementation of PET/CT radionuclide-based imaging methodology as a means to assess effective and temporal cardiac uptake represents a useful and critical application in drug development and pharmacological research and can be extended to the evaluation of comparable drug candidates.

Background: The left subclavian artery (LSA) is an infrequently used alternative access route for patients with severe peripheral artery disease (PAD) in patients who underwent transcatheter aortic valve replacement (TAVR). We report a new endovascular approach for TAVR combining an axillary prosthetic conduit-based access technique with new-generation balloon-expandable TAVR prostheses.Methods and Results: Between January 2020 and December 2020, 251 patients underwent TAVR at the West German Heart and Vascular Center. Of these, 10 patients (3.9%) were deemed to be treated optimally by direct surgical exposure of the left or right axillary artery via a surgically adapted prosthetic conduit. All procedures were performed under general anesthesia. One procedural stroke occurred due to severe calcification of the aortic arch. No specific complications of the subclavian access site (vessel rupture, vertebral, or internal mammary ischemia) were reported. Two minor bleedings from the access site could be treated conservatively. No surgical revision was necessary.Conclusion: The axillary prosthetic conduit-based access technique using new-generation balloon-expandable valves allows safe and successful TAVR in a subgroup of patients with a high risk of procedural complications due to severe peripheral vascular disease. Considering the increasing number of patients referred for TAVR, this approach could represent an alternative for patients with limited access sites.

Abstract Aims Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta‐analysis aims to assess the efficacy of beta‐blockers or angiotensin‐converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity. Methods and results We systematically searched Pubmed, Cochrane, EMBASE, and Web of Science databases for randomized controlled trials published until February 2019. The analysis included randomized studies that reported on left ventricular ejection fraction (LVEF) after 6 months of chemotherapy in cancer patients who received beta‐blockers or ACE inhibitors/ARBs for prevention of cardiotoxicity compared with controls. Studies on combination cardioprotective therapies were excluded from the analysis. The primary endpoint was prevention of a decrease in LVEF as defined by the individual study and as assessed by either transthoracic echocardiography or magnetic resonance imaging. We here show that patients under anthracycline‐based chemotherapy have a moderate yet significant benefit in LVEF from beta‐blockers or ACEs/ARBs. The beta‐blocker analysis included 769 cancer patients, and the ACE inhibitors/ARBs analysis included a total of 581 cancer patients. The mean LVEF difference between the beta‐blocker group and the control group was 2.57% (95% confidence interval 0.63–4.51, P = 0.009). The mean difference for ACE inhibitors/ARBs was 4.71% (95% confidence interval 0.38–9.03, P = 0.03). However, the beneficial effects throughout the studies were variable as documented by significant heterogeneity between the studies. Conclusions Systematic evidence is needed to solidly found recommendations for cardioprotective prevention during chemotherapy. Likewise, trials on other neurohumoral drugs (spironolactone) and lipid‐lowering approaches are required to improve protection for cardio‐oncology patients.

Detailed characterization of cardiac damage following ischemia/reperfusion injury and detection of occurring inflammatory responses is important for the development of new therapeutic concepts. Here the authors present a method for the three-dimensional investigation of acute and chronic cardiac injury responses using light sheet fluorescence microscopy.

Until recently, the visualization of cerebral microvessels was hampered by the fact that only short segments of vessels could be evaluated in brain sections by histochemistry. These limitations have been overcome by light sheet microscopy, which allows the 3D analysis of microvasculature in cleared brains. A major limitation of light sheet microscopy is that antibodies do not sufficiently penetrate cleared brains. We herein describe a technique of reverse clearing and rehydration, which after microvascular network analysis allows brain sectioning and immunohistochemistry employing a broad set of antibodies. Performing light sheet microscopy on brains of mice exposed to intraluminal middle cerebral artery occlusion (MCAO), we show that in the early phase of microvascular remodeling branching point density was markedly reduced, more strongly than microvascular length. Brain infarcts in light sheet microscopy were sharply demarcated by their autofluorescence signal, closely corresponding to brain infarcts revealed by Nissl staining. Neuronal survival, leukocyte infiltration, and astrocytic reactivity could be evaluated by immunohistochemistry in rehydrated brains, as shown in direct comparisons with non-cleared brains. Immunohistochemistry revealed microthrombi in ischemic microvessels that were likely responsible for the marked branching point loss. The balance between microvascular thrombosis and remodeling warrants further studies at later time-points after stroke.

Background: We aimed to describe whether updated low-density lipoprotein (LDL)-targets in patients with manifest coronary artery disease (CAD) led to a change in lipid profile over time. Methods: We retrospectively included patients with manifest CAD from 2009–2010, 2012–2013, and 2015–2016 (n = 500 each). Lipid levels and medication at the different time-points as well as rate of accordance to guidelines (

BackgroundThe 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.MethodsThis 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.ResultsIn 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 chemotherapy-induced cardiomyopathy than in patients without cardiotoxicity. Patients with positive cTnI and NT-proBNP were more likely to have a history of coronary heart disease, atrial fibrillation, and arterial hypertension.ConclusionOur data suggest that cardiac biomarkers play an important role in the detection of cancer therapy-induced cardiotoxicity. Larger systematic assessment in prospective cohorts is mandatory.

Background: Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease. We aimed to determine whether measures of left ventricular (LV) diastolic function and hypertrophy may predict presence of CMD. Methods: We retrospectively included patients undergoing diagnostic coronary angiography and transthoracic echocardiography, excluding patients with obstructive coronary artery disease, previous revascularization therapy, moderate or severe mitral valve disease, or atrial fibrillation. The following markers of LV diastolic function and hypertrophy were assessed: E- and A-wave velocity, E-wave deceleration time, E/A- and E/E′-ratio, left atrial area, left LV mass index, LV ejection time (LVET) and mitral valve closure to opening time. Logistic regression analysis was used to determine the association of echocardiographic parameters with presence of CMD. Results: From 378 patients (mean age ± SD 59.7 ± 13.6 years, 45.6% male) included, the majority had CMD (n = 293, 77.5%). Patients with CMD were older (60.5 ± 13.4 years vs. 56.9 ± 14.3 years, p = 0.03), were less frequent male (42.3% vs. 57.0%, p = 0.02), and had higher systolic blood pressure (137.9 ± 25.7 mmHg vs. 124.7 ± 25.6 mmHg, p

Abstract Background The pulsed electron avalanche knife (PEAK) PlasmaBlade™ is an innovative electrosurgical device that uses a novel technology to cut tissues. It has been proven to be safe and feasible in ear, nose, and throat surgery, but there are only limited data concerning the use of PlasmaBlade™ instead of conventional electrocautery in cardiac implantable electronic device (CIED) procedures except for generator replacements. Methods We conducted a retrospective, single-center study with patients undergoing CIED surgery at our center between December 2015 and March 2017 and evaluate the feasibility and the clinical outcome of the PlasmaBlade™. Results 282 patients (mean age 70.7 ± 12.9 years; 65.6% male) were included, of which 119 (42.2%) underwent pacemaker implantation, 95 (33.7%) implantable cardioverter defibrillator implantation, and 68 (24.1%) received a generator replacement. At the time of the procedure, 55 patients (19.5%) were on dual antiplatelet therapy, and 109 (38.7%) patients were on oral anticoagulation (30.5% vitamin K antagonists, 8.2% novel oral anticoagulants). The overall perioperative complication rate was 3.9%. Device-pocket hematoma occurred in 9 patients (3.2%) requiring further surgery. No lead damage was seen within a follow-up of 6 months. One patient presented with device-pocket infection 2.9 months after implantation of a cardiac resynchronization therapy defibrillator requiring CIED system extraction. Conclusions Replacing conventional electrocautery by PlasmaBlade™ for CIED procedures is feasible with a moderate rate of perioperative complications compared to the literature. Studies comparing the PlasmaBlade™ with conventional electrocautery are necessary to investigate whether PlasmaBlade™ offers an additional benefit over conventional electrocautery.

The improvement of anticancer-therapies results in a greater amount of long-term survivors after radiotherapy. Therefore, the understanding of cardiotoxicity after irradiation is of increasing importance. Cardiovascular adverse events after chest irradiation have been acknowledged for a long time but remain difficult to diagnose. Long-term cardiovascular adverse events may become evident years or decades after radiotherapy and the spectrum of potential cardiovascular side effects is large. Recent experimental and clinical data indicate that cardiovascular symptoms may be caused especially by heart failure with preserved ejection fraction, which remains incompletely understood in patients after radiation therapy. Heart radiation dose and co-existing cardiovascular risk factors represent some of the most important contributors for incidence and severity of radiation-induced cardiovascular side effects. In this review, we aim to elucidate the underlying patho-mechanisms and to characterize the development of radiation-induced cardiovascular damage. Additionally, approaches for clinical management and treatment options are presented.

Background: An increasing number of high-risk percutaneous coronary interventions (PCI) are performed with mechanical circulatory support (MCS) to minimize the risk of periprocedural hemodynamic compromise. Prior studies have demonstrated that an elevated left-ventricular end-diastolic pressure (LVEDP) is associated with worse outcome after acute myocardial infarction or cardiac surgery. Although LVEDP is frequently measured, little is known about the usefulness for predicting periprocedural hemodynamic deterioration in high-risk PCI. The objective of this study is to assess the impact of preprocedural measured LVEDP in non-shock patients undergoing high-risk PCI with MCS on periprocedural hemodynamic deterioration. Methods and Results: We reviewed the PCI protocol and the Automated Impella Controller in a consecutive series of 64 patients (mean age 73 years, 80% male), who underwent high-risk PCI with Impella MCS (period 01/2017–12/2018). LVEDP (17 ± 8 mm Hg) was measured in all cases before Impella insertion and start of PCI. Periprocedural hemodynamic deterioration was defined as: systolic blood pressure (SBP) drop (decrease ≥20 mm Hg or ≤90 mm Hg), or transient loss of arterial pressure pulsatility. Hemodynamic deterioration occurred in 33% (n = 21) of all patients but did not lead to a hemodynamic compromise due to the Impella support. Regression analysis of LVEDP for periprocedural hemodynamic deterioration or in-hospital major adverse cardiac and cerebrovascular events (MACCE) showed no significant results. Conclusion: LVEDP was not associated with periprocedural hemodynamic deterioration or a higher rate of in-hospital MACCE. Our data propose that LVEDP may not be used as a risk stratification variable for MCS usage in non-shock patients undergoing high-risk PCI. Keywords: Coronary artery disease, Impella, High-risk PCI, Mechanical circulatory support, Percutaneous coronary intervention

Immune checkpoint inhibitor (ICI) therapy has greatly improved treatment of various advanced cancers but increasing use of ICI therapy has exposed the risk of ICI-related cardiovascular side effects.Immune checkpoints are inhibitory regulators of T cell activation and mediate T cell effector functions during physiological responses to shield from autoimmune reactions. ICI therapy for advanced cancers promotes immune activity against tumors and is applied within a broad collective of cancer patients. Widespread use of ICI therapy has revealed the burden of immune related adverse events with various organ manifestations and characteristics. Since immune checkpoints are highly relevant for maintaining myocardial homeostasis as emerging evidence implicates, inhibition of immune checkpoint pathways has been associated with various forms of cardiotoxicity in preclinical models and patients. Although ICI-related cardiotoxicity is rare, it has significant relevance due to high mortality rates.This review focuses on current knowledge about cardiac ICI-related toxicity. We summarize the most common forms and delineate incidence, presentation, and treatment. Clinical characteristics are correlated to potential underlying pathomechanisms. We outline epidemiology, risk factors, and course of disease. Recommendations for monitoring and critical diagnostic measures are specified within the context of different forms of cardiac involvement. Different therapeutic implications for suspected ICI-related cardiotoxicity and their limitations are critically summarized.We highlight current gaps of knowledge concerning the underlying pathomechanisms and clinical characteristics of ICI-related cardiotoxicity. Future challenges are depicted for optimum cardio-oncology care of patients receiving ICI therapy. Keywords: Cardio-oncology, Cardiotoxicity, CTLA4, Immune checkpoint inhibitor, Myocarditis, PD1

BackgroundThe monoclonal antibody bevacizumab effectively inhibits angiogenesis in several types of cancers by blocking vascular endothelial growth factor. However, life‐threatening cardiovascular adverse effects could limit its use and may warrant specific follow‐up strategies. Methods and ResultsWe systematically searched MEDLINE, Cochrane, EMBASE, and Web of Science for randomized controlled trials published until November 2016 that assessed patients with cancer treated with or without bevacizumab in addition to standard chemotherapy. A total of 20 050 patients with a broad range of cancer types from 22 studies were included in this analysis (10 394 in the bevacizumab group and 9656 in the control group). The risks of arterial and venous adverse events were higher in the bevacizumab groups (relative risk [RR], 1.37; 95% CI, 1.10–1.70 [P=0.004] and RR, 1.29; 95% CI, 1.12–1.47 [P

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Several studies have found that standard risk scores inaccurately reflect risk in TAVI cohorts. The assessment of mortality risk upon post-interventional ICU admission is important to optimizing clinical management. This study sought to determine outcomes and factors affecting mortality in patients admitted to the intensive care unit (ICU) after transcatheter aortic valve implantation (TAVI), and to analyze and compare the predictive values of SAPS II and EuroSCORE.214 consecutive patients treated with transfemoral TAVI (2006-2012) admitted to the ICU in an academic tertiary-care university hospital, were included in this retrospective data analysis. The overall 30-day mortality rate was 7%. Non-survivors at 30-days and survivors showed differences in the rates of catecholamine therapy upon ICU admission (93 vs. 29%; p

BACKGROUND AND OBJECTIVE:Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO). NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR) suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR) approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR. METHODS AND RESULTS:Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%). Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03) and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p

End stage renal disease (ESRD) patients are characterized by increased morbidity and mortality due to highest prevalence of cardiovascular disease. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that controls cellular signaling in human physiology, pathophysiology, and diseases. Increased MIF plasma levels promote vascular inflammation and development of atherosclerosis. We have shown that MIF is associated with vascular dysfunction in ESRD patients. Whether hemodialysis (HD) affects circulating MIF plasma levels is unknown. We here aimed to investigate whether HD influences the circulating MIF pool in ESRD patients.An observational single-center study was conducted. MIF plasma levels in ESRD patients were assessed before, during, and after a HD session (n = 29). Healthy age-matched volunteers served as controls to compare correlations of MIF plasma levels with inflammatory plasma components (n = 20). MIF removed from the circulating blood pool could be detected in the dialysate and allowed for calculation of totally removed MIF (MIF content in dialysate 219±4 μg/HD-session). MIF plasma levels were markedly decreased 2 hour after initiation of HD (MIF plasma level pre-HD 84.8±6 ng/ml to intra-HD 61.2±5 ng/ml p

The systemic response to decreasing oxygen levels is hypoxic vasodilation. While this mechanism has been known for more than a century, the underlying cellular events have remained incompletely understood. Nitrite signaling is critically involved in vessel relaxation under hypoxia. This can be attributed to the presence of myoglobin in the vessel wall together with other potential nitrite reductases, which generate nitric oxide, one of the most potent vasodilatory signaling molecules. Questions remain relating to the precise concentration of nitrite and the exact dose-response relations between nitrite and myoglobin under hypoxia. It is furthermore unclear whether regulatory mechanisms exist which balance this interaction. Nitrite tissue levels were similar across all species investigated. We then investigated the exact fractional myoglobin desaturation in an ex vivo approach when gassing with 1% oxygen. Within a short time frame myoglobin desaturated to 58±12%. Given that myoglobin significantly contributes to nitrite reduction under hypoxia, dose-response experiments using physiological to pharmacological nitrite concentrations were conducted. Along all concentrations, abrogation of myoglobin in mice impaired vasodilation. As reactive oxygen species may counteract the vasodilatory response, we used superoxide dismutase and its mimic tempol as well as catalase and ebselen to reduce the levels of reactive oxygen species during hypoxic vasodilation. Incubation of tempol in conjunction with catalase alone and catalase/ebselen increased the vasodilatory response to nitrite. Our study shows that modest hypoxia leads to a significant nitrite-dependent vessel relaxation. This requires the presence of vascular myoglobin for both physiological and pharmacological nitrite levels. Reactive oxygen species, in turn, modulate this vasodilation response.