Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.

BACKGROUND: Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock despite a lack of evidence regarding its effect on mortality. METHODS: In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. RESULTS: A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P = 0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). CONCLUSIONS: In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov number, NCT03637205.).

Transcatheter valve repair of tricuspid regurgitation with the PASCAL system: TriCLASP study 30-day results.

BACKGROUND: Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. METHODS: TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. RESULTS: Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved ≤moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). CONCLUSION: Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and registered on ClinicalTrials.gov as NCT04614402. The current analysis is an interim report.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis.

Importance: The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear. Objective: To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women. Design, Setting, and Participants: Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies. Exposures: CAC score by computed tomography. Main Outcomes and Measures: Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated. Results: Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction. Conclusions and Relevance: Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.

Betablockers reduce oxygen pulse increase and performance in heart failure patients with preserved ejection fraction.

BACKGROUND: Beta blockers (BB) reduce chronotropic response and exercise capacity in heart failure with preserved ejection fraction (HFpEF). To analyze the influence of BB on exercise performance and O 2 pulse increase as a surrogate for stroke volume in HFpEF. METHODS: We retrospectively analyzed the influence of BB intake (yes: n = 48/no: n = 51) on peak oxygen uptake (VO 2peak), oxygen uptake efficiency slope (OUES), and increase of O 2 pulse in HFpEF patients undergoing cardiopulmonary exercise testing (CPET). Associations of outcome variables and risk category of the algorithm of the Heart Failure Association of the European Society of Cardiology (HFA-PEFF score) were calculated. RESULTS: Patients on BB showed lower VO 2peak (p = .003) and OUES (p = .002), with a dominant effect in the high-risk (p = .020; 0.002), but not in the low risk-group (p = .434; p = .499). In the intermediate group BB showed a trend towards lower VO 2peak (p = .078) and lower values for OUES (p = .020). Patients on BB also demonstrated a lower increase of O 2 pulse during exercise (p = .002), without differences between HFA-PEFF risk groups (low: p = .322, intermediate: p = .269, high: p = .313). CONCLUSIONS: BB reduce exercise capacity and O 2 pulse increase in HFpEF patients. Direct quantification of O 2 pulse increase may help to improve the discrimination of HFpEF patients.

High- vs. Low-Intensity Statin Therapy and Changes in Coronary Artery Calcification Density after One Year.

Background: Statin therapy promotes the progression of coronary artery calcification (CAC). Comparing patients on high (HIST) vs. low-to-intermediate intensity statin therapy (LIST), randomized controlled trials with a one-year follow-up failed to document a relevant difference in the Agatston score and CAC volume. We evaluated whether statin intensity modifies CAC density at one year. Methods: We performed a pooled analysis of two randomized-controlled trials (BELLES, EBEAT), comparing the effects of HIST (Atorvastatin 80 mg) vs. LIST (Pravastatin 40 mg, Atorvastatin 10 mg) on CAC measures after one year. The differences in CAC density and its change were compared using the two-sided t-test. Results: Data from 852 patients (66.7% female) with available baseline and follow-up CT were evaluated from both trials. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: −45.8 ± 38.5 vs. −72.9 ± 46.0 mg/dL, p < 0.001). Mean CAC density increased from 228.8 ± 35.4 HU to 232.6 ± 37.0 HU (p < 0.0001) at one-year follow-up. Comparing patients on HIST vs. LIST, CAC density at follow-up (HIST: 231.9 ± 36.1 HU vs. LIST: 233.3 ± 37.7 HU, p = 0.59) and its change from baseline (HIST: 4.0 ± 19.1 HU vs. LIST: 3.6 ± 19.6 HU, p = 0.73) did not differ. Subgroup analyses, stratifying by LDL reduction (

Differences in treatment strategies for LDL-cholesterol reduction in a university lipid clinic vs. standard care apart from the use of PCSK9 inhibitors.

BACKGROUND: Lipid-lowering therapy (LLT) in patients with cardiovascular disease (CVD) is insufficient despite clear guideline recommendations. Lipid clinics have specialized in patients with dyslipidemia, but the magnitude and reduction of low-density lipoprotein cholesterol (LDL-C) in lipid clinics has not yet been studied in depth. OBJECTIVE: To assess LDL-C reduction in very high-risk CVD patients achieved in a lipid clinic through different forms of LLT in comparison to standard care without the initiation of PSCK9 inhibitors. METHODS: Data from 96 lipid clinic patients were analyzed retrospectively and compared to 84 standard care patients. Very high-risk patients were defined according to the European Society of Cardiology (ESC). Different combinations of LLT focusing on statins and ezetimibe were investigated. Achievement of LDL-C treatment goals according to ESC guidelines as well as LDL-C reduction were assessed. RESULTS: Baseline and follow-up data of 180 very high-risk CVD patients (mean age 67.7 (±9.8) y; 60.6% male) were used. Achievement of the LDL-C goal in lipid clinic patients increased significantly from 14.6% at baseline to 41.7% at the latest visit (p<0.001) while standard care patients improved from 21.4% to 33.3% (p=0.08). The largest relative LDL-C reduction via an adjustment in LLT was achieved by initiation of high-intensity statins (50.8 ± 4.9%, n = 5, p < 0.05). CONCLUSION: Treatment in a lipid clinic leads to a superior LDL-C goal achievement in very high-risk CVD patients as compared to standard care with the highest reduction under LLT with high-intensity statins and ezetimibe. Referral algorithms have to be established for high-risk patients.

The degree of permanent pacemaker dependence and clinical outcomes following transcatheter aortic valve implantation: implications for procedural technique.

Aims: Conduction abnormalities necessitating permanent pacemaker (PPM) implantation remain the most frequent complication post-transcatheter aortic valve implantation (TAVI), yet reliance on PPM function varies. We evaluated the association of right-ventricular (RV)-stimulation rate post-TAVI with 1-year major adverse cardiovascular events (MACE) (all-cause mortality and heart failure hospitalization). Methods and results: This retrospective cohort study of patients undergoing TAVI in two high-volume centers included patients with existing PPM pre-TAVI or new PPM post-TAVI. There was a bimodal distribution of RV-stimulation rates stratifying patients into two groups of either low [≤10%: 1.0 (0.0, 3.6)] or high [>10%: 96.0 (54.0, 99.9)] RV-stimulation rate post-TAVI. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated comparing MACE in patients with high vs. low RV-stimulation rates post-TAVI. Of 4659 patients, 408 patients (8.6%) had an existing PPM pre-TAVI and 361 patients (7.7%) underwent PPM implantation post-TAVI. Mean age was 82.3 ± 8.1 years, 39% were women. A high RV-stimulation rate (>10%) development post-TAVI is associated with a two-fold increased risk for MACE [1.97 (1.20, 3.25), P = 0.008]. Valve implantation depth was an independent predictor of high RV-stimulation rate [odds ratio (95% CI): 1.58 (1.21, 2.06), P=<0.001] and itself associated with MACE [1.27 (1.00, 1.59), P = 0.047]. Conclusion: Greater RV-stimulation rates post-TAVI correlate with increased 1-year MACE in patients with new PPM post-TAVI or in those with existing PPM but low RV-stimulation rates pre-TAVI. A shallower valve implantation depth reduces the risk of greater RV-stimulation rates post-TAVI, correlating with improved patient outcomes. These data highlight the importance of a meticulous implant technique even in TAVI recipients with pre-existing PPMs.

Clinical characteristics and determinants of mortality in coronavirus disease 2019 (COVID-19) patients on an intensive care unit-a retrospective explorative 1-year all-comers study.

Background: Clinical outcome in patients with coronavirus disease 2019 (COVID-19) requiring treatment on intensive care units (ICU) remains unfavourable. The aim of this retrospective study was to exploratively identify potential predictors of unfavourable outcome in ICU patients diagnosed with COVID-19. Methods: In all patients with COVID-19 (n=50) or severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) as comorbidity (n=11) at our ICU we assessed clinical, respiratory and laboratory parameters with a potential role for outcome. Main outcome variables were intubation and mortality rates. Results: Between March 2020 and March 2021, 573 patients were hospitalized with SARS-CoV-2 infection. Of these, 61 patients (10.6%, 44.3% women) aged 66.4±13.3 were admitted to ICU. A proportion of 73.8% of patients had moderate or severe acute respiratory distress syndrome (ARDS). COVID-19 patients differed clinically from those with SARS-CoV-2 as comorbidity, such as severe heart or renal failure or sepsis as the leading cause of ICU admission, despite similar mortality rates (44.0% vs. 45.5%, P>0.5). Among COVID-19 patients, those who died had more often severe ARDS (91% vs. 46%, P=0.001), longer non-invasive ventilation (NIV) therapy prior to ICU (6.3±5.9 vs. 2.5±2.0 days, P=0.046), and higher interleukin-6 (IL-6) and lactate dehydrogenase (LDH) values as compared to survivors. In multivariable analysis, NIV duration ≥5 days on admission [odds ratio (OR): 42.20, 95% confidence interval (CI): 1.22 to >99, P=0.038] and IL-6 [OR: 4.08, 95% CI: 1.16-14.33, P=0.028] remained independently predictive of mortality. In worsening tertiles of partial pressure of oxygen (pO2)/inspiratory oxygen fraction (FiO2) on admission (≥161.5, 96.5 to <161.5, <96.5) we observed a stepwise increase in intubation rates (P=0.0034) and mortality rates (P=0.031). Conclusions: As inflammation, ARDS severity and longer NIV duration prior to ICU are associated with intubation and mortality rates, prognosis appears to be largely determined by disease severity. Whether NIV aggravates ARDS or if it indicates lack of recovery independent from type of ventilation, or both should be clarified in a prospective trial.

Income-Related Peripheral Artery Disease Treatment: A Nation-Wide Analysis from 2009-2018.

Economic status has a measurable and significant effect on cardiovascular health. Socioeconomic- and income-related disparities worsen cardiovascular risk factors. Peripheral artery disease (PAD) remains a major risk factor for morbidity and mortality. Not all patients benefit equally from recent advances in outpatient healthcare. The implementation of guideline recommendations regarding treatment is inadequate. Income-related disparities for PAD treatment are unknown. We aimed to analyse income-stratified PAD prevalence, outpatient treatment and pharmacotherapy. Associations of statutory health insurance physicians at the regional level, income-stratified PAD prevalence and differences in outpatient care and pharmacotherapy were analysed in 70.1 million statutorily insured patients/year between 2009 and 2018. Analysis was based on claims data (§295 of the social code (SGB V)) and drug-prescription data (§300 SGB V). The diagnosis of PAD was defined by ICD I70.2-9. Regional income data were derived from the German Census Bureau. PAD prevalence was higher in low-income than in high-income areas. Low-income patients more often presented to angiology outpatient care and more frequently received guideline recommended pharmacotherapy. High-income patients more often presented to outpatient vascular surgery. This was true for statins, antiplatelets, intermittent claudication and critical limb ischemia alike. These data indicate that PAD and income are associated. Regional income is related to insufficiencies in guideline-recommended treatment and contact to vascular specialists. Our results aim to encourage medical professionals to implement PAD guideline recommendations, especially in high-income areas. Further studies on associations between spatial-level income and healthcare in PAD are needed.

Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction - a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study.

BACKGROUND: Epicardial adipose tissue (EAT) surrounds the heart and the coronary vessels. EAT produces pro- and anti-inflammatory cytokines. Several studies have already documented the association of EAT and cardiovascular risk factors as well as coronary artery disease manifestations. Currently computed tomography (CT) is considered the gold standard for measurement of 3-dimensional volume of EAT. In addition, echocardiography might be an easy accessible alternative in particular in an emergency setting. METHODS: We performed a metaanalysis of existing studies describing the differences of EAT in patients with and without myocardial infarction. We used established databases and were searching for "epicardial adipose tissue" or "pericardial adipose tissue" and "myocardial infarction", "coronary events", or "acute coronary syndrome". We included over 6600 patients from 7 studies. Random effect models were calculated and all analyses were performed by using the Review Manager 5.3. RESULTS: Patients with myocardial infarction had 37% (confidence interval [0.21-0.54], P value <.001)] higher measures of EAT compared to patients without myocardial infarction. Comparing studies using echocardiography vs CT for assessment of EAT thickness, similar relative differences in EAT with wide overlap of confidence intervals were observed (for echocardiography: 0.4 [0.04-0.76], for CT: 0.36 [0.16-0.57], P value <.001 for both). CONCLUSIONS: Patients with myocardial infarction have more EAT as compared to patients without myocardial infarction independently of the used imaging modality. Further prospective studies are needed to evaluate, how quantification of EAT in clinical routine can improve patients management.

Socioeconomic position is associated with N-terminal pro-brain natriuretic peptide (NT-proBNP)-Results of the population-based Heinz Nixdorf Recall study.

OBJECTIVES: N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. METHODS: Baseline data of 4598 participants aged 45-75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. RESULTS: With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. CONCLUSIONS: In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

Air Pollution and Progression of Atherosclerosis in Different Vessel Beds-Results from a Prospective Cohort Study in the Ruhr Area, Germany.

OBJECTIVES: Due to inconsistent epidemiological evidence on health effects of air pollution on progression of atherosclerosis, we investigated several air pollutants and their effects on progression of atherosclerosis, using carotid intima media thickness (cIMT), coronary calcification (CAC), and thoracic aortic calcification (TAC). METHODS: We used baseline (2000-2003) and 5-y follow-up (2006-2008) data from the German Heinz Nixdorf Recall cohort study, including 4,814 middle-aged adults. Residence-based long-term air pollution exposure, including particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), (PM10), and nitrogen dioxide (NO2) was assessed using chemistry transport and land use regression (LUR) models. cIMT was quantified as side-specific median IMT assessed from standardized ultrasound images. CAC and TAC were quantified by computed tomography using the Agatston score. Development (yes/no) and progression of atherosclerosis (change in cIMT and annual growth rate for CAC/TAC) were analyzed with logistic and linear regression models, adjusting for age, sex, lifestyle variables, socioeconomic status, and traffic noise. RESULTS: While no clear associations were observed in the full study sample (mean age 59.1 (±7.6) y; 53% female), most air pollutants were marginally associated with progression of atherosclerosis in participants with no or low baseline atherosclerotic burden. Most consistently for CAC, e.g., a 1.5 µg/m3 higher exposure to PM2.5 (LUR) yielded an estimated odds ratio of 1.19 [95% confidence interval (CI): 1.03, 1.39] for progression of CAC and an increased annual growth rate of 2% (95% CI: 1%, 4%). CONCLUSION: Our study suggests that development and progression of subclinical atherosclerosis is associated with long-term air pollution in middle-aged participants with no or minor atherosclerotic burden at baseline, while overall no consistent associations are observed. https://doi.org/10.1289/EHP7077.

Troponins and Natriuretic Peptides in Cardio-Oncology Patients-Data From the ECoR Registry.

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 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. CONCLUSION: Our 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.

Novel anticoagulants versus vitamin K antagonists for cardioversion of non- valvular atrial fibrillation - a meta-analysis of more than 17000 patients.

Non-vitamin K antagonist oral anticoagulants (NOACs) have proven a favorable risk-benefit profile compared to vitamin K antagonists (VKAs) for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but actual data are not sufficiently powered to extend this profile on patients with AF that undergo cardioversion. We aimed to compare outcomes after cardioversion of AF under NOACs vs. VKAs. We systematically searched Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies published until October 2017. A total of 17506 patients from 11 studies were included. Treatment with NOACs was associated with similar relative risks (RR) of stroke and systemic embolism, hemorrhagic stroke, myocardial infarction, cardiovascular death, and all cause death compared to VKAs treatment. The RR of ischemic stroke was lower in the NOACs group. The risk of major bleeding was similar across treatment groups. Treatment with NOACs in patients with non-valvular AF that undergo cardioversion seems to be as safe and effective as the use of classical VKAs, with a better profile for ischemic stroke. Clinical Trial Registration: PROSPERO Registry, CRD42018086181 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 86181 .

Cardiovascular imaging in cardio-oncology.

Cancer therapy may lead to cardiovascular complications and can promote each aspect of cardiac disease manifestation, such as vascular disease including coronary heart disease, myocardial diseases including heart failure, structural heart diseases including valvular heart diseases, and rhythm disorders. All potential complications of cancer therapy onto the cardiovascular system require imaging for diagnostic workup as well as monitoring of therapy. Transthoracic echocardiography (TTE) is the most frequently used tool for assessment of cardiac function during or after cancer therapy in daily clinical routine. With modern techniques like strain analysis, echocardiography allows to detect a variety of cardiac diseases as caused by cancer therapy even at subclinical stages. For further workup, specific imaging techniques including nuclear imaging are needed in a multimodality imaging approach to in detail characterize the underlying pathophysiology and to improve the management of the patients. Therefore, the field of imaging in cardio-oncology is rapidly growing. This review article will give an overview about existing literature regarding the role of imaging in the diagnostic evaluation and management of therapy in patient with prior or ongoing cancer therapy.

Comparison of Lipoprotein(a)-Levels in Patients ≥70 Years of Age With Versus Without Aortic Valve Stenosis.

Although lipoprotein(a) (Lp[a]) is linked with aortic valve calcification and clinical aortic valve stenosis (AVS) in middle-aged cohorts, patients aged ≥70 years represent a majority of patients with AVS, in which mechanisms leading to AVS may differ. We sought to determine whether Lp(a) distinguishes patients ≥70 years with and without AVS. We matched 484 patients ≥70 years with AVS, scheduled for transcatheter aortic valve implantation with 484 patients without AVS by age group and gender. Lp(a) levels were compared in patients with and without AVS and stratified by presence and absence of clinical coronary artery disease (CAD) manifestation. A total of 968 patients (mean age 80 ± 5 years, 48% women) were included. When comparing patients with and without AVS, no difference in Lp(a) was observed (AVS: 17 [8; 56] mg/dl, no AVS: 18.5 [8.5; 57] mg/dl, p = 0.56). In contrast, patients with clinical CAD manifestation had higher Lp(a) levels than those without clinical CAD manifestation (coronary artery disease: 19 [9; 60] mg/dl, no coronary artery disease 15 [7; 44] mg/dl, p = 0.0006). In regression analysis, no significant association of Lp(a) with AVS was observed in unadjusted (OR [95% CI]: 0.98 [0.91 to 1.06], p = 0.59) and risk factor-adjusted models (0.98 [0.90 to 1.06], p = 0.57). However, Lp(a) was independently associated with clinical CAD manifestation (unadjusted: 1.14 [1.04 to 1.24], p = 0.003, risk factor adjusted: 1.17 [1.07 to 1.27], p = 0.0006). In conclusion, in a large cohort of patients ≥70 years, Lp(a) was associated with clinical CAD manifesation, but not with AVS. Our results suggest that in patients over 70 years, the development of AVS is not influenced by Lp(a).

Sleep characteristics and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall cohort study.

BACKGROUND AND AIMS: Sleep characteristics are associated with incident cardiovascular diseases (CVD), but there is a lack of studies on the association between sleep characteristics and incidence/progression of coronary artery calcification (CAC). METHODS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at baseline 45-74 years; 47% men), we fitted logistic and linear regression models to assess associations between self-rated sleep characteristics (nocturnal and total sleep duration; napping; various sleep disorders) and CAC incidence/CAC progression. Progression was measured as 5-year progression factor, as categories of absolute CAC change, and additionally characterized as rapid or slow compared to an extrapolation of baseline CAC values. RESULTS: We observed barely any association between sleep characteristics and CAC progression regardless of the chosen statistical approach; associations between sleep and CAC incidence were slightly larger, e.g., the geometric mean of the 5-year CAC progression factor was 6.8% (95% confidence interval: -9.5; 25.9) larger for ≤5 h, 2.9% (-7.3; 14.3) larger for 5.1-6.9 h and 7.1% (-2.4; 15.7) smaller for ≥7.5 h total sleep compared to 7- <7.5 h total sleep. For subjects with any regular sleep disorder, the geometric mean of the 5-year CAC progression was 3.5% (-4.7; 11.2) smaller compared to subjects without any regular sleep disorder. CONCLUSIONS: In this German cohort study, sleep characteristics were barely associated with CAC progression.

Cardiac computed tomography-derived epicardial fat volume and attenuation independently distinguish patients with and without myocardial infarction.

BACKGROUND AND OBJECTIVE: Epicardial adipose tissue (EAT) volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction. METHODS AND RESULTS: In 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male) undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28) had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07) and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03) than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02). EAT volume increased per standard deviation of age (18.2 [6.2-30.2] ml, p = 0.003), BMI (29.3 [18.4-40.2] ml, p<0.0001), and with presence of diabetes (44.5 [16.7-72.3] ml, p = 0.0002), while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08-4.61] HU, p = 0.04). In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10-2.94], p = 0.02 for volume, 2.04 [1.18-3.53], p = 0.01 for attenuation). Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77-2.68], p = 0.26 for volume; 1.93 [1.11-3.39], p = 0.02 for attenuation). CONCLUSION: CT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.

Accuracy of a diagnostic strategy combining aortic dissection detection risk score and D-dimer levels in patients with suspected acute aortic syndrome.

AIMS: The European Society of Cardiology recently proposed a novel diagnostic algorithm combining the aortic dissection detection (ADD) risk score with D-dimer level assessment for detecting acute aortic syndromes (AASs) in patients presenting with chest pain. The diagnostic accuracy of this strategy is yet to be validated. METHODS: We retrospectively identified 376 patients with chest pain and available D-dimer on admission to the emergency department of our institution between January 2011 and May 2014. The ADD risk score was calculated using retrospective blinded chart review. A score ⩽1 was defined as 'low probability', whereas a score >1 as 'high probability'. AASs were diagnosed in 85 (22.6%) patients. RESULTS: Patients with AAS more frequently had a 'high probability' score than AAS-negative patients (63.5% vs 1.0%; P<0.001). An ADD risk score ⩾1 had a sensitivity of 98.8% and a specificity of 64.6% for diagnosing AAS with a failure rate of 0.5%, whereas an ADD risk score ⩾2 had a sensitivity of 63.5% and a specificity of 98.9% with a failure rate of 9.7%. Among the patients with a 'low probability' score, D-dimer had a sensitivity and specificity for the detection of AAS, respectively, of 93.5% and 63.2%, with a negative predictive value of 98.9% and a failure rate of 1.1%. CONCLUSIONS: A 'high probability' ADD score detected AAS with good specificity. A 'low probability' score combined with negative D-dimer safely and efficiently ruled out AAS with a low failure rate.