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.

Acute coronary occlusion with vs. without ST-elevation: impact on procedural outcomes and long-term all-cause mortality.

BACKGROUND: Acute total occlusion (ATO) is diagnosed in a substantial proportion of patients with Non-ST-elevation myocardial infarction (NSTEMI). We compared procedural outcomes and long- term mortality in patients with ST-elevation myocardial infarction (STEMI) with NSTEMI with vs. without ATO. METHODS: We included patients with acute myocardial infarction undergoing invasive coronary angiography between 2004 and 2019 at our center. ATO was defined as TIMI 0-1 flow in the infarct-related artery or TIMI 2-3 flow with highly elevated peak troponin (>100-folds the upper reference limit). Association between presentation and long-term mortality was evaluated using multivariable adjusted Cox regression analysis. RESULTS: From 2269 acute myocardial infarction patients (mean age 66 ± 13.2 years, 74% male), 664 patients with STEMI and 1605 patients with NSTEMI (471 [29.3%] with ATO) were included. ATO(+)NSTEMI had higher frequency of cardiogenic shock and no-reflow than ATO(-)NSTEMI with similar rates compared to STEMI patients (cardiogenic shock: 2.76 vs. 0.27 vs. 2.86%, p < 0.0001, p = 1; no-reflow: 4.03 vs. 0.18 vs. 3.17%, p < 0.0001, p = 0.54). ATO(+)NSTEMI and STEMI were associated with 60% and 55% increased incident mortality, as compared to ATO(-)NSTEMI (ATO(+)NSTEMI: 1.60[1.27-2.02], p < 0.0001, STEMI: 1.55[1.24-1.94], p < 0.0001). Likewise, left ventricular ejection fraction (48.5 ± 12.7 vs. 49.1±11 vs. 50.6 ± 11.8%, p = 0.5, p = 0.018) and global longitudinal strain (-15.2±-5.74 vs. -15.5±-4.84 vs. -16.3±-5.30%, p = 0.48, p = 0.016) in ATO(+)NSTEMI were comparable to STEMI but significantly worse than in ATO(-)NSTEMI. CONCLUSION: NSTEMI patients with ATO have unfavorable procedural outcomes, resulting in increased long-term mortality, resembling STEMI. Our findings suggest that the occlusion perspective provides more appropriate classification of acute myocardial infarction than differentiation into STEMI vs. NSTEMI.

NET-Induced Carcinoid Heart Disease Affecting Both Tricuspid and Aortic Valves Due to Patent Foramen Ovale and Right/Left Shunt: A Multi-imaging Challenge to Nuclear Medicine.

ABSTRACT: Carcinoid heart disease (Hedinger syndrome) is a long-term consequence in hormone-active neuroendocrine tumors with hepatic metastases and carcinoid syndrome. Because of serotonin, excess multiple cardiac and pulmonary symptoms evolve, which are further complicated by a patent foramen ovale due to right-left shunting. We present a 53-year-old man with an ileum-neuroendocrine tumor including gross liver metastases and long-term stable disease who subsequently developed Hedinger syndrome. Initially experiencing progressive dyspnea, he eventually experienced severe hypoxemia due to patent foramen ovale. 99mTc-MAA lung perfusion scintigraphy quantitatively identified the right-left shunting, whereas 68Ga-FAPI-46 PET/CT characterized the typical fibrous heart valve thickening due to serotonin-induced fibroblast proliferative properties.

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.

Hand grip strength in patients with advanced cancer: A prospective study.

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 <20.0 kg/m2 with ≥2% weight loss (Fearon's criteria). Cox proportional hazard analyses were performed to assess the relationship of maximal HGS to all-cause mortality and to determine cut-offs for HGS with the best predictive power. We also assessed associations with additional relevant clinical and functional outcome measures at baseline, including anthropometric measures, physical function (Karnofsky Performance Status and Eastern Cooperative of Oncology Group), physical activity (4-m gait speed test and 6-min walk test), patient-reported outcomes (EQ-5D-5L and Visual Analogue Scale appetite/pain) and nutrition status (Mini Nutritional Assessment). RESULTS: The mean age was 60 ± 14 years; 163 (51%) were female, and 148 (44%) had cachexia at baseline. Patients with cancer showed 18% lower HGS than healthy controls (31.2 ± 11.9 vs. 37.9 ± 11.6 kg, P < 0.001). Patients with cancer cachexia had 16% lower HGS than those without cachexia (28.3 ± 10.1 vs. 33.6 ± 12.3 kg, P < 0.001). Patients with cancer were followed for a mean of 17 months (range 6-50), and 182 (55%) patients died during follow-up (2-year mortality rate 53%) (95% confidence interval 48-59%). Reduced maximal HGS was associated with increased mortality (per -5 kg; hazard ratio [HR] 1.19; 1.10-1.28; P < 0.0001; independently of age, sex, cancer stage, cancer entity and presence of cachexia). HGS was also a predictor of mortality in patients with cachexia (per -5 kg; HR 1.20; 1.08-1.33; P = 0.001) and without cachexia (per -5 kg; HR 1.18; 1.04-1.34; P = 0.010). The cut-off for maximal HGS with the best predictive power for poor survival was <25.1 kg for females (sensitivity 54%, specificity 63%) and <40.2 kg for males (sensitivity 69%, specificity 68%). CONCLUSIONS: Reduced maximal HGS was associated with higher all-cause mortality, reduced overall functional status and decreased physical performance in patients with mostly advanced cancer. Similar results were found for patients with and without cancer cachexia.

Epicardial adipose tissue and obstructive coronary artery disease in acute chest pain: the EPIC-ACS study.

Aims: We tested the hypothesis that epicardial adipose tissue (EAT) quantification improves the prediction of the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department. Methods and results: Within this prospective observational cohort study, we included 657 consecutive patients (mean age 58.06 ± 18.04 years, 53% male) presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, haemodynamic instability, or known CAD were excluded. As part of the initial workup, we performed bedside echocardiography for quantification of EAT thickness by a dedicated study physician, blinded to all patient characteristics. Treating physicians remained unaware of the results of the EAT assessment. The primary endpoint was defined as the presence of obstructive CAD, as detected in subsequent invasive coronary angiography. Patients reaching the primary endpoint had significantly more EAT than patients without obstructive CAD (7.90 ± 2.56 mm vs. 3.96 ± 1.91 mm, P < 0.0001). In a multivariable regression analysis, a 1 mm increase in EAT thickness was associated with a nearby two-fold increased odds of the presence of obstructive CAD [1.87 (1.64-2.12), P < 0.0001]. Adding EAT to a multivariable model of the GRACE score, cardiac biomarkers and traditional risk factors significantly improved the area under the receiver operating characteristic curve (0.759-0.901, P < 0.0001). Conclusion: Epicardial adipose tissue strongly and independently predicts the presence of obstructive CAD in patients presenting with acute chest pain to the emergency department. Our results suggest that the assessment of EAT may improve diagnostic algorithms of patients with acute chest pain.

Effect of visual presentation of atherosclerotic carotid plaque on adherence to secondary preventive therapy using mHealth technologies (PreventiPlaque app): Study protocol for a randomized controlled trial.

Background: Cardiovascular disease is the major cause of death worldwide. Although knowledge regarding diagnosing and treating cardiovascular disease has increased dramatically, secondary prevention remains insufficiently implemented due to failure among affected individuals to adhere to guideline recommendations. This has continued to lead to high morbidity and mortality rates. Involving patients in their healthcare and facilitating their active roles in their chronic disease management is an opportunity to meet the needs of the increasing number of cardiovascular patients. However, simple recall of advice regarding a more preventive lifestyle does not affect sustainable behavioral lifestyle changes. We investigate the effect of plaque visualization combined with low-threshold daily lifestyle tasks using the smartphone app PreventiPlaque to evaluate change in cardiovascular risk profile. Methods: and study design: This randomized, controlled clinical trial includes 240 participants with ultrasound evidence of atherosclerotic plaque in one or both carotid arteries, defined as focal thickening of the vessel wall measuring 50% more than the regular vessel wall. A criterion for participation is access to a smartphone suitable for app usage. The participants are randomly assigned to an intervention or a control group. While both groups receive the standard of care, the intervention group has additional access to the PreventiPlaque app during the 12-month follow-up. The app includes daily tasks that promote a healthier lifestyle in the areas of smoking cessation, medication adherence, physical activity, and diet. The impact of plaque visualization and app use on the change in cardiovascular risk profile is assessed by SCORE2. Feasibility and effectiveness of the PreventiPlaque app are evaluated using standardized and validated measures for patient feedback. Ethics and dissemination: This clinical trial is approved by the ethics committee of the University of Duisburg-Essen (Germany). Study results will be disseminated at conferences and in peer-reviewed journals. Information regarding the PreventiPlaque app is available via print media, social media channels, and on the authors' websites.

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.

Impact of socioeconomic and cardiovascular risk factors on the effect of genetic variants associated with NT-proBNP.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an established biomarker for diagnosis of heart failure. The study aims to explore whether known cardiovascular risk factors, including education and income as indicators of socioeconomic position (SEP), may interact with the genetic effect of NT-proBNP-related single nucleotide polymorphisms (SNP) to influence plasma levels of NT-proBNP in a population-based study sample. Information on effect alleles of three SNPs previously reported to be related to NT-proBNP was combined individually for 4,520 participants of the Heinz Nixdorf Recall Study to calculate a genetic risk allele sum score (GRSNT-proBNP). Linear Regression models were used to examine the association of cardiovascular risk factors and GRSNT-proBNP with log-transformed NT-proBNP levels, as well as cardiovascular risk factor by GRSNT-proBNP interactions. The GRSNT-proBNP was associated with NT-proBNP showing 1.13-fold (95% CI 1.10-1.16) higher plasma levels per additional effect allele. Interaction terms included in the regression models gave some indication for interaction of the GRSNT-proBNP with the SEP indicator income as well as with C-reactive protein. In regression models stratified by income quartiles the strongest genetic effect was observed in the third income quartile showing 1.18-fold (95% CI 1.12-1.25) higher average NT-proBNP levels per additional allele compared to the lowest income quartile with 1.08-fold (95% CI 1.01-1.15) higher NT-proBNP levels. The results of the present study indicate that genetic effects of NT-proBNP increasing alleles are stronger in higher SEP groups. This may be due to a stronger influence of non-genetic cardiovascular risk on NT-proBNP in low SEP groups.

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.

Higher BNP/NT-pro BNP levels stratify prognosis equally well in patients with and without heart failure: a meta-analysis.

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 < 0.0001). The effect sizes were comparable, with a substantial overlap in the confidence intervals, when comparing studies involving patients with and without heart failure (1.75[1.54-2.0], P < 0.0001 vs. 1.74[1.47-2.06], P < 0.0001). Similar results were observed when stratifying by quartiles of BNP/NT-proBNP. In studies using pre-defined cut-off-values for BNP/NT-proBNP, elevated levels were associated with the long-term prognosis, independent of the specific cut-off value used. CONCLUSIONS: BNP/NT-proBNP levels are predictors for adverse long-term outcome in patients with and without known heart failure. Further research is necessary to establish appropriate thresholds, especially in non-heart failure cohorts.

Gender Differences in Outpatient Peripheral Artery Disease Management in Germany: A Population Based Study 2009-2018.

OBJECTIVE: Peripheral artery disease (PAD) is a major risk factor for morbidity and death. Despite clear guideline recommendations regarding outpatient treatment and pharmacotherapy, implementation is inadequate. Gender differences are becoming increasingly important, especially in patients with atherosclerosis. METHODS: Gender stratified PAD prevalence and differences in treatment by specialised outpatient care and pharmacotherapy were analysed in 70.1 million statutorily insured patients/year in Germany between 2009 and 2018. This was based on claims data according to §295 of the social code (SGB V) and drug prescription data according to §300 SGB V. Diagnosis of PAD was defined according to ICD I70.2-9 coding. Statistical analysis was performed with the chi square test for trend and two way ANOVA. RESULTS: In total, 17 633 970 patients with PAD were identified, of whom 47% were female. Prevalence of PAD in Germany increased between 2009 and 2018 and was higher in male patients. Only a minority of 37.1% presented to a vascular specialist. Interestingly, female patients were both less likely to present to a vascular specialist and to receive guideline recommended pharmacotherapy. Overall prescription rates of statins and antiplatelet drugs increased between 2009 and 2018, however. PAD stages were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI). In CLTI even fewer patients received a statin, with the gender gap increasing. CONCLUSION: The results demonstrate gender based differences in pharmacotherapy and specialised outpatient care of patients with PAD. While overall outpatient treatment by vascular specialists and guideline recommended medical therapy of PAD are low, women and patients with CLTI remain undertreated.

Epicardial fat and incident heart failure with preserved ejection fraction in patients with coronary artery disease.

BACKGROUND: We aimed to determine, whether epicardial adipose tissue (EAT) as local source of inflammation, as well as its change over time, associates with the development of heart failure with preserved ejection fraction (HFpEF) in patients with coronary artery disease. METHODS AND RESULTS: We retrospectively included 379patients (aged 65.2 ± 11.7 years, 70.2%male) with coronary artery disease but without heart failure at baseline, undergoing clinical and echocardiographic assessment in 2010-2013 and receiving a second assessment in 2014-2018. EAT thickness was defined as space between the myocardium and the pericardium and indexed (EATi) by body surface area. Change in EATi was calculated as the difference of follow-up and baseline EATi. HFpEF was defined according to presence of dyspnea, elevated natriuretic peptides, and structural and/or functional alterations on echocardiography in accordance with current European Society of Cardiology guidelines. During a median follow-up of 4.3 years, 142patients (37.5%) developed HFpEF. Patients with onset of HFpEF had higher EATi at baseline (2.4 ± 1.3 vs. 1.9 ± 0.9 mm/m2, p = 0.001). In multivariable regression analysis, EATi associated with onset of HFpEF (1.25 [1.01-1.54], p = 0.04). Likewise, an increase in EATi over time was linked HFpEF development, independent of other risk factors and baseline EATi (1.39 [1.04-1.87], p = 0.03). EATi was significantly associated with follow-up b-type natriuretic peptide (BNP) levels (4.31[0.58-8.05], p = 0.024), but not with baseline BNP (2.24[-0.27-4.76], p = 0.08). CONCLUSION: EATi is associated with the development of HFpEF. The finding of changes in EATi altering the risk of HFpEF manifestation support the rationale for further research on epicardial fat modulation as a treatment target for HFpEF.

Left Ventricular Diastolic Function Following Anthracycline-Based Chemotherapy in Patients with Breast Cancer without Previous Cardiac Disease-A Meta-Analysis.

BACKGROUND: Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognised that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterisation. METHODS: Studies reporting on echocardiographic diastolic function parameters before and after ANT in breast cancer patients without cardiac disease were included. We evaluated pulsed wave (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e') and E/e' ratio) echocardiographic parameters. RESULTS: A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT while EDT was not influenced by ANT. Additionally, e' and E/e' ratio showed no significant change after ANT. A modest reduction in LV ejection fraction and global longitudinal strain was observed at the end of ANT therapy. CONCLUSIONS: ANT had a modest early impact on E/A ratio, without changing EDT, e', or E/e' in patients with breast cancer without cardiac disease. Randomised studies on larger populations, using new parameters are required to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity.

Peripheral artery disease in Germany (2009-2018): Prevalence, frequency of specialized ambulatory care and use of guideline-recommended therapy - A population-based study.

BACKGROUND: Peripheral artery disease (PAD) patients have high morbidity and mortality rates, demonstrating a need for improved treatment strategies. While underuse and undertreatment have been reported, there is no clear picture of patterns in population-level disease prevalence, prescription of guideline-recommended pharmacotherapy, or frequency of contact with dedicated specialists. We present population-level data on changes in prevalence, care and treatment of PAD from 2009 to 2018 in Germany. METHODS: We analyzed the ambulatory claims data for all statutorily insured patients comprising 70.1 million patients each year and 87% of the German population. Prevalence was assessed by documentation of PAD and stratified by age and sex within the 10-year study timeframe. In addition, current ambulatory care, stratified by vascular specialists (vascular surgeons or angiologists), internists, cardiologists and primary care physicians, were examined. FINDINGS: Prevalence increased from 1·85% in 2009 to 3·14% in 2018, affecting 2·3 million patients in 2018 and more males (55%) than females (45%). A low level of visits to vascular specialists, with 11·1% receiving care from vascular surgeons and 8·1% from angiologists, was shown. Moreover, analysis of guideline-recommended prescriptions revealed increasing, but still insufficient, prescription frequencies among PAD patients between 2009 and 2016, from 42·6% to 56% for statins and from 40·2% to 48·0% for antiplatelets. INTERPRETATION: Our results show that the prevalence of PAD in Germany, as assessed by outpatient PAD documentation, is increasing and PAD patients are underutilizing specialized vascular care; moreover, the prescription frequency of guideline-recommended therapies remains low. There is a clear need to improve the referral and treatment algorithms in the high-risk PAD population. FUNDING: None.

Risk stratification and mortality prediction in octo- and nonagenarians with peripheral artery disease: a retrospective analysis.

OBJECTIVES: Among changes in demographics, aging is the most relevant cardiovascular risk factor. The prevalence of peripheral artery disease (PAD) is high in elderly patients and is associated with a worse prognosis. Despite optimal treatments, mortality in the high-risk population of octo- and nonagenarians with PAD remains excessive, and predictive factors need to be identified. The objective of this study was to investigate predictors of mortality in octo- and nonagenarians with PAD. METHODS: Cases of treated octo- and nonagenarians, including the clinical characteristics and markers of myocardial injury and heart failure, were studied retrospectively with respect to all-cause mortality. Hazard ratios [HR] were calculated and survival was analyzed by Kaplan-Meyer curves and receiver operating characteristic curved were assessed for troponin-ultra and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and chronic limb-threatening ischemia (CLTI). RESULTS: A total of 123 octo- and nonagenarians admitted for PAD were eligible. The troponin level was the major predictor of all-cause mortality (HR: 4.6, 95% confidence interval [CI]: 1.4-15.3), followed by the NT-proBNP level (HR: 3.9, 95% CI 1.8-8.8) and CLTI (HR: 3.1, 95% CI 1.6-5.9). Multivariate regression revealed that each increment of 1 standard deviation in log troponin and log NT-proBNP was associated with a 2.7-fold (95% CI 1.8-4.1) and a 1.9-fold (95% CI 1.2-2.9) increased risk of all-cause death. Receiver operating characteristic curve analysis using a combination of all predictors yielded an improved area under the curve of 0.888. In a control group of an equal number of younger individuals, only NT-proBNP (HR: 4.2, 95% CI 1.2-14.1) and CLTI (HR: 6.1, 95% CI 1.6-23.4) were predictive of mortality. CONCLUSION: Our study demonstrates that cardiovascular biomarkers and CLTI are the primary predictors of increased mortality in elderly PAD patients. Further risk stratification through biomarkers in this high-risk population of octo- and nonagenarians with PAD is necessary.

Apixaban versus PhenpRocoumon: Oral AntiCoagulation plus antiplatelet tHerapy in patients with Acute Coronary Syndrome and Atrial Fibrillation (APPROACH-ACS-AF): Rationale and design of the prospective randomized parallel-group, open-label, blinded-endpoint, superiority, multicenter-trial of a triple therapy versus a dual therapy in patients with Atrial Fibrillation and Acute Coronary Syndrome undergoing coronary stenting.

BACKGROUND: A regimen of dual (DAT) vs. triple (TAT) antithrombotic therapy reduces bleeding in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, recent evidence suggests that DAT may be associated with an increased ischemic risk. This raises the question whether DAT rather than TAT should be recommended to AF patients that undergo PCI for acute coronary syndrome (ACS), carrying a particularly high risk of both bleeding and ischemic events, studied only as subgroups of previous trials. METHODS AND DESIGN: The APPROACH-ACS-AF-(DZHK-7) trial is a multicenter prospective, randomized, open-label, blinded endpoint (PROBE) trial which will include patients presenting with an ACS managed by PCI and requiring oral anticoagulation (OAC) due to AF. The trial will test, whether a DAT-regimen comprising clopidogrel plus the non-Vitamin-K-antagonist oral anticoagulant (NOAC) apixaban is superior to a TAT-regimen of vitamin-K-antagonist (VKA) plus dual anti-platelet therapy (APT) with respect to bleeding. A total of 400 patients will be randomized 1:1 to a control-arm with guideline-recommended TAT with VKA plus clopidogrel and acetylsalicylic-acid and a study arm receiving DAT comprising apixaban plus clopidogrel. Patients will be followed-up for 6 months. The primary endpoint of the study is the cumulative incidence of BARC type ≥2 bleeding, secondary endpoints include a composite clinical ischemic outcome and net clinical outcome. CONCLUSIONS: APPROACH-ACS-AF is the first trial dedicated to ACS patients, testing whether in terms of bleeding a DAT with NOAC is superior to a TAT regimen with VKA in high-risk ACS patients with AF.