Mansoor's Self-Report Tool for Cardiovascular Risk Assessment predicts adverse in-hospital events in patients with pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening acute disease accompanied by high morbidity and mortality. Regarding hospitalizations of patients with PE, risk stratification of these patients is crucial. Thus, risk stratification tools like risk scores are of key interest. METHODS: The nationwide German inpatient sample of the years 2005-2018 was used for this present analysis. Hospitalized PE patients were stratified according to Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class, and the performance of this score was evaluated to predict adverse in-hospital events. RESULTS: Overall, 1 174 196 hospitalizations of PE patients (53.5% females; 56.4% ≥70 years) were registered in Germany between 2005 and 2018. According to the Mansoor's self-report tool for cardiovascular risk assessment, 346 126 (29.5%) PE patients were classified as high risk. Higher Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class was predictive for in-hospital death (OR 1.129 [95%CI 1.117-1.141], P < 0.001), shock (OR 1.117 [95%CI 1.095-1.140], P < 0.001), cardiopulmonary resuscitation (OR 1.109 [95%CI 1.092-1.126], P < 0.001), right ventricular dysfunction (OR 1.039 [95%CI 1.030-1.048], P < 0.001), intracerebral bleeding (OR 1.316 [95%CI 1.275-1.358], P < 0.001), and gastro-intestinal bleeding (OR 1.316 [95%CI 1.275-1.358], P < 0.001). Systemic thrombolysis was not associated with lower in-hospital mortality in high-risk class (OR 5.139 [95%CI 4.961-5.323], P < 0.001). CONCLUSIONS: Prognostic performance of the Mansoor's Self-Report Tool for Cardiovascular Risk Assessment for risk stratification of PE patients was poor and not able to identify those PE patients, who might benefit from systemic thrombolysis. However, the Mansoor's Self-Report Tool for Cardiovascular Risk Assessment was moderately helpful to identify PE patients at higher risk for bleeding events.

Incidence and impact of venous thromboembolism in hospitalized patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is associated with an increased risk for venous thromboembolism (VTE). Beside higher VTE risk, data on impact of VTE on survival and risk factors for the occurrence of VTE in CD are sparse. METHODS: The German nationwide inpatient sample was screened for patients admitted due to CD (ICD-code K50). CD hospitalizations were stratified for VTE and risk-factors for VTE and impact of VTE on in-hospital case-fatality rate were investigated. RESULTS: Overall, 333,975 hospitalizations of patients due to CD were counted in Germany (median age 38.0 [IQR 24.0-52.0] years, 56.0 % females) during the observational period 2005-2018. VTE rate increased slightly from 0.6 % (2005) to 0.7 % (2018) (ß 0.000097 [95%CI 0.000027 to 0.000167], P = 0.007) 2005-2018 and with age-decade (ß 0.0017 [95%CI 0.0016 to 0.0019], P < 0.001). In total, 0.7 % (2295) of the CD inpatients had a VTE event. Patients with VTE were in median 12 years older (49.0 [34.0-62.0] vs. 37.0 [24.0-52.0] years, P < 0.001) and colon-involvement was in those patients more prevalent (32.0 % vs.27.7 %, P < 0.001). Age ≥ 70 years, obesity, colon-involvement, cancer, surgery, thrombophilia, and heart failure were strongly associated with higher risk of VTE in CD patients. In-hospital death occurred 15-times more often in CD with VTE than without (4.5 % vs. 0.3 %, P < 0.001). VTE was independently associated with increased in-hospital case-fatality rate (OR 9.31 [95%CI 7.54-11.50], P < 0.001). CONCLUSIONS: VTE is a life-threatening event in hospitalized CD patients associated with 9.3-fold increased case-fatality rate. Older age, obesity, colon involvement, cancer, surgery, thrombophilia and heart failure were strong risk factors for VTE in CD.

Risk Factors for Pulmonary Embolism in Patients with Paralysis and Deep Venous Thrombosis.

BACKGROUND: Venous thromboembolism is a frequent complication and an important cause of death in patients with paralysis. We aimed to investigate predictors of pulmonary embolism (PE) and the impact of PE on the survival of patients with paralysis in comparison to those with deep venous thrombosis or thrombophlebitis (DVT). METHODS: Patients were selected by screening the German nationwide inpatient sample (2005-2017) for paralysis, and were stratified for venous thromboembolism (VTE) and the VTE-sub-entity PE (ICD-code I26). Impact of PE on mortality and predictors for PE were analyzed. RESULTS: Overall, 7,873,769 hospitalizations of patients with paralysis were recorded in Germany 2005-2017, of whom 1.6% had VTE and 7.0% died. While annual hospitalizations increased (2005: 520,357 to 2017: 663,998) (ß 12,421 (95% CI 10,807 to 14,034), p < 0.001), in-hospital mortality decreased from 7.5% to 6.7% (ß -0.08% (95% CI -0.10% to -0.06%), p < 0.001). When focusing on 82,558 patients with paralysis hospitalized due to VTE (51.8% females; 58.3% aged ≥ 70 years) in 2005-2017, in-hospital mortality was significantly higher in patients with paralysis and PE than in those with DVT only (23.8% vs. 6.3%, p < 0.001). Cancer (OR 2.18 (95% CI 2.09-2.27), p < 0.001), heart failure (OR 1.83 (95% CI 1.76-1.91), p < 0.001), COPD (OR 1.63 (95% CI 1.53-1.72), p < 0.001) and obesity (OR 1.42 (95% CI 1.35-1.50), p < 0.001) were associated with PE. PE (OR 4.28 (95% CI 4.07-4.50), p < 0.001) was a strong predictor of in-hospital mortality. CONCLUSIONS: In Germany, annual hospitalizations of patients with paralysis increased in 2005-2017, in whom VTE and especially PE substantially affected in-hospital mortality. Cancer, heart failure, COPD, obesity and acute paraplegia were risk factors of PE.

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism.

BACKGROUND: An increased risk for venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep venous thrombosis, has been reported in psoriasis patients. The impact of psoriasis on prognosis of VTE patients is widely unknown. METHODS: Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome was investigated in the German nationwide inpatient sample of the years 2005-2017. RESULTS: Overall, 1,076,384 hospitalizations of PE patients (53.7% females, median age 72.0 [60.0-80.0] years) were recorded in Germany 2005-2017. Among these, 3145 patients had psoriasis (0.3%). Psoriatic PE patients were younger (68.0 [57.0-76.0] vs. 72.0 [60.0-80.0] years,P < 0.001) and more often male (64.1% vs. 46.3%,P < 0.001). The prevalence of VTE risk factors, traditional cardiovascular risk factors and cardiovascular comorbidities was higher in psoriatic than in non-psoriatic individuals. Psoriatic PE patients showed a lower in-hospital case-fatality rate (11.1% vs. 16.0%,P < 0.001), confirmed by logistic regressions showing an independent association of psoriasis with reduced case-fatality rate (OR 0.73 [95%CI 0.65-0.82],P < 0.001), despite higher prevalence of pneumonia (24.8% vs. 23.2%,P = 0.029). Psoriasis was an independent predictor for gastro-intestinal bleeding (OR 1.35 [95%CI 1.04-1.75],P = 0.023) and transfusion of blood constituents (OR 1.23 [95%CI 1.11-1.36],P < 0.001). CONCLUSIONS: PE patients with psoriasis were hospitalized in median four years earlier than those without. Although psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile in PE patients, our data demonstrate a lower in-hospital mortality in psoriatic PE, which might be mainly driven by younger age. Our findings may improve the clinical management of these patients and contribute evidence for relevant systemic manifestation of psoriasis. TRANSLATIONAL PERSPECTIVE: An increased risk for venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep venous thrombosis, has been reported in psoriasis patients, but the impact of psoriasis on prognosis of VTE patients is widely unknown. PE patients with psoriasis were younger and psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile. In-hospital mortality was lower in psoriatic PE patients, which might be mainly driven by younger age. Our findings improve the clinical management of PE patients and contribute evidence for relevant systemic manifestation of psoriasis. ONE SENTENCE SUMMARY: Psoriasis with chronic inflammation promotes PE development, is associated with an unfavorable cardiovascular and VTE-risk profile, but lower in-hospital mortality.

Temporal trends and predictors of inhospital death in patients hospitalised for heart failure in Germany.

AIMS: We investigated trends in incidence, case fatality rate, patient characteristics and adverse inhospital events of patients hospitalised for heart failure in Germany. METHODS AND RESULTS: The German nationwide inpatient sample (2005-2016) was used for this analysis. Patients hospitalised due to heart failure were selected for analysis. Temporal trends in the incidence of hospitalisations, case fatality rate and treatments were analysed and predictors of inhospital death were identified. The analysis comprised a total number of 4,539,140 hospitalisations (52.0% women, 81.0% aged ≥70 years) due to heart failure. Although hospitalisations increased from 381 (2005) to 539 per 100,000 population (2016) (ß estimate 0.06, 95% confidence interval (CI) 0.06 to 0.07, P < 0.001) in parallel with median age and prevalence of comorbidities, the inhospital case fatality rate decreased from 11.1% to 8.1% (ß estimate -0.36, 95% CI -0.37 to -0.35, P < 0.001) and the rate of major adverse cardiovascular and cerebrovascular events (ß estimate -0.24, 95% CI -0.25 to -0.23, P < 0.001) decreased from 12.7% to 10.3%. Age 70 years and older (odds ratio (OR) 2.60, 95% CI 2.57 to 2.63, P < 0.001) and cancer (OR 1.93, 95% CI 1.91 to 1.96, P < 0.001) were independent predictors of inhospital death. CONCLUSION: Hospitalisations for heart failure increased in Germany from 2005 to 2016, whereas the major adverse cardiovascular and cerebrovascular event rate and inhospital case fatality rate decreased during this period despite higher patient age and increasing prevalence of comorbidities.

Predictive value of the Kuijer score for bleeding and other adverse in-hospital events in patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) constitute a major global burden of disease. Current international guidelines recommend treatment with anticoagulant therapy after VTE for a duration of at least 3 months. Since anticoagulation also imposes an increased risk for bleeding events, the individual risk has to be evaluated to determine adequate treatment plans. METHODS: The nationwide German inpatient sample of the years 2005-2017 was used for this analysis. Hospitalized VTE patients were stratified according to Kuijer risk class and the performance of the Kuijer score was evaluated to predict adverse in-hospital events. RESULTS: Overall, 1,204,895 VTE patients were treated between 2005 and 2017 in Germany and were included in the present study (839,143 patients had deep venous thrombosis and/or thrombophlebitis and 669,881 patients pulmonary embolism). According to Kuijer risk class stratification, in total, 176,723 (14.7%) of the hospitalized VTE patients were classified as low risk, 914,964 (75.9%) as intermediate risk and 113,208 (9.4%) as high risk. A higher Kuijer risk class was predictive for in-hospital death (odds ratio [OR] 1.99 [95% confidence interval (CI) 1.96-2.02], P < 0.001), major adverse cardiovascular and cerebrovascular events (MACCE, OR 1.90 [95%CI 1.87-1.93], P < 0.001), intracerebral bleeding (OR 1.28 [95%CI 1.14-1.44], P < 0.001), gastrointestinal bleeding (OR 1.56 [95%CI 1.48-1.64], P < 0.001) as well as necessity of transfusion of blood constituents (OR 2.94 [95%CI 2.88-3.00], P < 0.001) independently of important comorbidities. CONCLUSIONS: The Kuijer score is an important risk stratification tool to predict individual risk regarding in-hospital outcomes comprising major bleeding events such as intracerebral bleeding and necessity of transfusion of blood constituents, but also in-hospital mortality and MACCE in VTE patients.

Impact of obesity on adverse in-hospital outcomes in patients undergoing percutaneous mitral valve edge-to-edge repair using MitraClip® procedure - Results from the German nationwide inpatient sample.

BACKGROUND AND AIM: The number of percutaneous edge-to-edge mitral regurgitation (MR) valve repairs with MitraClip® implantations increased exponentially in recent years. Studies have suggested an obesity survival paradox in patients with cardiovascular diseases. We investigated the influence of obesity on adverse in-hospital outcomes in patients with MitraClip® implantation. METHODS AND RESULTS: We analyzed data on characteristics of patients and in-hospital outcomes for all percutaneous mitral valve repairs using the edge-to-edge MitraClip®-technique in Germany 2011-2015 stratified for obesity vs. normal-weight/over-weight. The nationwide inpatient sample comprised 13,563 inpatients undergoing MitraClip® implantations. Among them, 1017 (7.5%) patients were coded with obesity. Obese patients were younger (75 vs.77 years,P < 0.001), more often female (45.4% vs.39.5%,P < 0.001), had more often heart failure (87.1% vs.79.2%,P < 0.001) and renal insufficiency (67.0% vs.56.4%,P < 0.001). Obese and non-obese patients were comparable regarding major adverse cardiac and cerebrovascular events (MACCE) and in-hospital death. The combined endpoint of cardio-pulmonary resuscitation (CPR), mechanical ventilation and death was more often reached in non-obese than in obese patients with a trend towards significance (20.6%vs.18.2%,P = 0.066). Obesity was an independent predictor of reduced events regarding the combined endpoint of CPR, mechanical ventilation and death (OR 0.75, 95%CI 0.64-0.89,P < 0.001), but not for reduced in-hospital mortality (P = 0.355) or reduced MACCE rate (P = 0.108). Obesity class III was associated with an elevated risk for pulmonary embolism (OR 5.66, 95%CI 1.35-23.77,P = 0.018). CONCLUSIONS: We observed an obesity paradox regarding the combined endpoint of CPR, mechanical ventilation and in-hospital death in patients undergoing MitraClip® implantation, but our results failed to confirm an impact of obesity on in-hospital survival or MACCE.

Impact of concomitant deep or superficial venous thrombosis of the legs on survival of patients with pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a frequent cause of death and morbidity. A few studies suggest that clot burden in pulmonary artery bed is related to PE patients' survival, but the impact of concomitant deep venous thrombosis and/or thrombophlebitis (DVT) on short-term survival of PE patients remains unclear. Thus, we aimed to investigate the impact of DVT on adverse outcomes in PE patients. METHODS: Patients of the nationwide inpatient sample with PE (ICD-code I26) were stratified for DVT (ICD-code I80) and compared for patient characteristics, risk stratification markers, treatments and outcomes. Impact of concomitant DVT on adverse in-hospital outcomes was tested. RESULTS: Overall, 346,586 PE patients (53.3% females) were included in this analysis. Among these, in 126,477 (36.5%) DVT was coded. PE patients with DVT were younger, less often of female sex and VTE risk-factors (surgery, cancer) as well as cardiovascular and pulmonary diseases were less prevalent compared with isolated PE. PE patients with DVT showed a significant better survival (5.4% vs. 20.2%, P < .001) and lower adverse in-hospital event rate (9.7% vs. 27.4%, P < .001) compared to patients with isolated PE. Lower risk for in-hospital mortality (OR 0.238 [95%CI 0.232-0.245], P < .001) and adverse in-hospital events (OR 0.302 [95%CI 0.295-0.309], P < .001) were respectively independent of age, gender, comorbidities and reperfusion-treatments. CONCLUSIONS: Concomitant DVT affects survival of PE patients. Patients with an isolated PE had higher rate of in-hospital mortality and adverse in-hospital events. Our data suggest, that peripheral thrombus burden in PE with concomitant DVT might be less harmful in comparison to isolated PE with a probably larger thrombus burden.

Sex-specific differences drive temporal trends and outcomes of patients hospitalized for heart failure in Germany.

BACKGROUND: Despite remarkable improvements in treatment of cardiovascular disease, heart failure (HF) is still characterized by high mortality rate. Sex-specific differences in HF have been described, but underlying reasons are widely unexplored. METHODS: The nationwide German inpatient sample (2005-2016) was used for this sex-specific analyses. Temporal trends on hospitalizations, mortality, and treatments were analysed and independent predictors of adverse outcomes identified. RESULTS: The analysis comprises 4,538,977 hospitalizations due to HF (52.0%women) in Germany (2005-2016). Although women were older (median 82(IQR75-87) vs.76(69-82),P < 0.001), coronary artery disease (CAD, 50.3% vs. 30.7%,P < 0.001) was more prevalent in men, who were more often treated with percutaneous intervention (PCI;3.4% vs. 1.4%,P < 0.001) and implantable cardioverter-defibrillator (2.2% vs. 0.5%,P < 0.001). In-hospital mortality was significantly lower in men than in women (8.9% vs.10.2%,P = 0.001) and was reduced in patients who received PCI or implantation of an implantable cardioverter-defibrillator. While total numbers of hospitalizations between 2005 and 2016 increased in both men (ß-estimate 7185.71 (95%CI 6502.23 to 7869.18),P < 0.001) and women (ß-estimate 5297.60 (95%CI 4557.37 to 6037.83),P < 0.001) as well as almost all comorbid co-conditions, in-hospital mortality rate decreased more distinctly in women (ß-estimate -0.41 (95%CI -0.42 to -0.39),P < 0.001) compared to men (ß-estimate -0.29 (95%CI -0.30 to -0.27),P < 0.001). CONCLUSIONS: Interventional treatments of HF were associated with improved outcomes and equally beneficial for both sexes. However, they were more often used in male HF patients, in which CAD is significantly more frequent than in female HF patients. This may explain the higher case fatality rate of HF in females.

Impact of atrial fibrillation/flutter on the in-hospital mortality of ischemic stroke patients.

BACKGROUND: Stroke is the second leading cause of death worldwide. Ischemic strokes, which are caused by atrial fibrillation/flutter (AF), may be more devastating than those that occur without AF. OBJECTIVE: The purpose of this study was to investigate the impact of AF on adverse events in hospitalized ischemic stroke patients and to estimate the elevated impact of AF on the occurrence of these adverse events. METHODS: The nationwide German inpatient sample of the years 2005-2015 was used for this analysis. Ischemic stroke patients were identified by ICD code I63 and stratified by AF. Logistic regression models were used to investigate the impact of AF on adverse in-hospital events and adjusted for age, sex, and comorbidities to prove the independence of the associations. RESULTS: Overall, 2,958,697 hospitalized ischemic stroke patients (50.5% female, 65.4% age >70 years) were included in the analysis. Of these patients, 849,466 (28.7%) were diagnosed with AF. Overall, 9.0% of the stroke patients died in-hospital. The case fatality rate increased with age and was higher in stroke patients with AF than in those without AF (13.0% vs 7.3%; P <.001). AF was an important predictor of in-hospital death (odds ratio 1.30; 95% confidence interval 1.28-1.31; P <.001) and adverse events during hospitalization, independent of age, sex, and comorbidities. Deterioration of patient prognosis due to AF was especially pronounced in younger patients. CONCLUSION: AF in ischemic stroke patients is associated with higher in-hospital mortality and higher rate of adverse events during hospitalization, independent of age, sex, and comorbidities.

Survival Benefit of Obese Patients With Pulmonary Embolism.

OBJECTIVE: To investigate the impact of obesity and underweight on adverse in-hospital outcomes in pulmonary embolism (PE). PATIENTS AND METHODS: Patients diagnosed as having PE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification code I26 in the German nationwide inpatient database were stratified for obesity, underweight, and normal weight/overweight (reference group) and compared regarding adverse in-hospital outcomes. RESULTS: From January 1, 2011, through December 31, 2014, 345,831 inpatients (53.3% females) 18 years and older were included in this analysis; 8.6% were obese and 0.5% were underweight. Obese patients were younger (67.0 vs 73.0 years), were more frequently female (60.2% vs 52.7%), had a lower cancer rate (13.6% vs 20.5%), and were more often treated with systemic thrombolysis (6.4% vs 4.3%) and surgical embolectomy (0.3% vs 0.1%) vs the reference group (P<.001 for all). Overall, 51,226 patients (14.8%) died during in-hospital stay. Obese patients had lower mortality (10.9% vs 15.2%; P<.001) vs the reference group and a reduced odds ratio (OR) for in-hospital mortality (OR, 0.74; 95% CI, 0.71-0.77; P<.001) independent of age, sex, comorbidities, and reperfusion therapies. This survival benefit of obese patients was more pronounced in obesity classes I (OR, 0.56; 95% CI, 0.52-0.60; P<.001) and II (OR, 0.63; 95% CI 0.58-0.69; P<.001). Underweight patients had higher prevalence of cancer and higher mortality rates (OR, 1.15; 95% CI, 1.00-1.31; P=.04). CONCLUSION: Obesity is associated with decreased in-hospital mortality rates in patients with PE. Although obese patients were more often treated with reperfusion therapies, the survival benefit of obese patients occurred independently of age, sex, comorbidities, and reperfusion treatment.

5-Year Experience of In-Hospital Outcomes After Percutaneous Left Atrial Appendage Closure in Germany.

OBJECTIVES: The aim of this study was to evaluate 5-year in-hospital trends and safety outcomes of left atrial appendage (LAA) closure in the German nationwide inpatient sample. BACKGROUND: The safety and efficacy of percutaneous LAA closure have been demonstrated in randomized trials and prospective cohort studies, but results from large samples are missing. METHODS: Data on patient characteristics and in-hospital safety outcomes for all percutaneous LAA closures performed in Germany between 2011 and 2015 were analyzed. Overall, 15,895 inpatients were included. RESULTS: The annual number of LAA occlusions increased from 1,347 in 2011 to 4,932 in 2015 (ß = 1.00; 95% confidence interval [CI]: 0.95 to 1.01; p < 0.001), with a nonsignificant uptrend of in-hospital mortality (from 0.5% in 2011 to 0.9% in 2015; ß = 0.01; 95% CI: -0.09 to 0.32; p = 0.271). Patient characteristics shifted toward older age and higher prevalence of comorbidities such as heart failure, chronic obstructive pulmonary disease, and chronic renal insufficiency over time. Important independent predictors of in-hospital mortality were cancer (odds ratio [OR]: 2.49; 95% CI: 1.00 to 6.12; p = 0.050), heart failure (OR: 2.42; 95% CI: 1.72 to 3.41; p < 0.001), stroke (OR: 5.39; 95% CI: 2.76 to 10.53; p < 0.001), acute renal failure (OR: 13.28; 95% CI: 9.08 to 19.42; p < 0.001), pericardial effusion (OR: 5.65; 95% CI: 3.76 to 8.48; p < 0.001), and shock (OR: 45.11; 95% CI: 31.01 to 65.58; p < 0.001). CONCLUSIONS: The use of percutaneous LAA closure increased 3.6-fold from 2011 to 2015, with a nonsignificant uptrend of in-hospital mortality rate in this real-world setting. Important predictors of in-hospital death were acute renal failure, pericardial effusion, and ischemic stroke during hospitalization.

Incidence of infective endocarditis before and after the guideline modification regarding a more restrictive use of prophylactic antibiotics therapy in the USA and Europe.

Infective endocarditis (IE) is a potentially life-threatening disease. Regardless the improvements in IE management, it remains associated with high mortality and severe complications. Staphylococci and streptococci account for 80% of all IE cases. Prevention of IE by appropriate administration of antibiotics before procedures with potential bacteremia in selected patients is recommended according to recent and current guidelines. However, recent studies, have questioned the efficacy of antimicrobial prophylaxis in special situations and in some patient-groups. As a consequence, the guideline of the French working group on IE in 2002, the American Heart Association (AHA) guideline in 2007, the National Institute for Health and Clinical Excellence (NICE) guideline for Great Britain in 2008, and the European Society of Cardiology (ESC) guideline in 2009 restricted the recommendation for antibiotic prophylaxis to high-risk patients only, and only for certain invasive procedures. IE incidence increased in the USA, England and Germany in the last two decades. Study results for the USA, England, France, and Germany were not consistent regarding the influence of the revised guidelines for IE prophylaxis on the IE incidence. Although some study results pointed to an increase of the IE cases after the changes in the guideline recommendations, a final appraisal regarding the impact of the revised guideline recommendations on IE incidence could not be drawn at this time point due to the heterogeneous study results.

Incidence and in-hospital safety outcomes of patients undergoing percutaneous mitral valve edge-to-edge repair using MitraClip: five-year German national patient sample including 13,575 implants.

AIMS: The number of percutaneous edge-to-edge mitral regurgitation valve repairs with MitraClip implantation has increased during recent years. Published studies showed promising safety outcomes in relatively small cohorts, while results from large samples are sparse. Thus, we aimed to evaluate trends and safety outcomes in the German nationwide in-patient sample. METHODS AND RESULTS: We analysed data on patients' characteristics and in-hospital safety outcomes for all percutaneous mitral valve repairs using the MitraClip technique in Germany between 2011 and 2015. Overall, 13,575 in-patients were included. The annual number of MitraClip implantations increased from 815 in 2011 to 4,432 in 2015 (ß 1.00 [95% CI: 0.96-1.03], p<0.001). The in-hospital mortality (p=0.193) and major adverse cardiac and cerebrovascular events (MACCE) (p=0.183) rate remained unchanged. Important independent predictors of in-hospital mortality were heart failure (OR 1.91 [95% CI: 1.43-2.54], p<0.001), transfusion of erythrocyte concentrates (OR 9.04 [95% CI: 7.45-10.96], p<0.001), stroke (OR 6.82 [95% CI: 4.34-10.72], p<0.001), endocarditis (OR 19.52 [95% CI: 9.04-42.14], p<0.001), pulmonary embolism (OR 7.61 [95% CI: 3.44-16.81], p<0.001), pericardial tamponade (OR 14.08 [95% CI: 7.09-27.96], p<0.001) and pericardial effusion (OR 2.59 [95% CI: 1.66-4.04], p<0.001). CONCLUSIONS: MitraClip implantations increased markedly (5.4-fold) between 2011 and 2015, with a constant in-hospital mortality and MACCE rate. Our data indicate that edge-to-edge mitral valve repair using the MitraClip technique has acceptable in-hospital safety outcomes in a real-world scenario.

Temporal Trends in the Prevalence of Infective Endocarditis in Germany Between 2005 and 2014.

Infective endocarditis (IE) is a potentially life-threatening disease. Little is known about temporal trends in its prevalence in Germany. In 2009, recommendations for antibiotic prophylaxis were deescalated in the revised European Society of Cardiology guideline to include only patients at high risk of IE. We selected patients with the discharge diagnosis of IE based on the International Classification of Diseases code I33 in the nationwide database of the Federal Statistical Office of Germany. We identified 94,364 patients with a diagnosis of IE from January 2005 to December 2014. Mean prevalence was 11.6 per 100,000 citizens per year in this 10-year-period. The annual IE prevalence showed a continuous small increase from 2006 to 2010 (9.5 to 10.6 IE diagnoses per 100,000 citizens) and a larger increase from 2011 to 2014 (11.1 to 14.4 IE diagnoses per 100,000 citizens; linear regression: ß 2.9, 95% confidence interval 1.1 to 4.6; p = 0.006). The prevalence of IE in Germany was lower compared to the United States but higher compared to England. Overall, 15,995 patients (17%) died in hospital. Case fatality rate after a diagnosis of IE remained largely constant from 2005 to 2014. In conclusion, the annual prevalence of IE continuously increased during the observed period with more pronounced trend after the revised 2009 European Society of Cardiology guideline.

Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: a novel mechanism underlying vasospastic angina.

A 37-year old male patient presented with frequent angina attacks (up to 40/day) largely resistant to classical vasodilator therapy. The patient showed severe coronary and peripheral endothelial dysfunction, increased platelet aggregation and increased platelet-derived superoxide production. The endothelial nitric oxide synthase (eNOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) reduced superoxide formation in platelets identifying "uncoupled" eNOS as a superoxide source. Oral L-arginine normalized coronary and peripheral endothelial dysfunction and reduced platelet aggregation and eNOS-derived superoxide production. Plasma concentrations of the endogenous NOS inhibitor asymmetric dimethyl-L-arginine (ADMA), representing an independent risk factor for cardiovascular disease, were normal in the patient. However, immediately after oral administration of cationic amino acid (CAA), plasma ADMA levels rose markedly, demonstrating increased ADMA efflux from intracellular stores. ADMA efflux from mononuclear cells of the patient was accelerated by CAA, but not neutral amino acids (NAA) demonstrating impairment of y(+)LAT (whose expression was found reduced in these cells). These data suggest that impairment of y(+)LAT may cause intracellular (endothelial) ADMA accumulation leading to systemic endothelial dysfunction. This may represent a novel mechanism underlying vasospastic angina and vascular dysfunction in general. Moreover, these new findings contribute to the understanding of the l-arginine paradox, the improvement of eNOS activity by oral L-arginine despite sufficient cellular l-arginine levels to ensure proper function of this enzyme.

Monitoring white blood cell mitochondrial aldehyde dehydrogenase activity: implications for nitrate therapy in humans.

Recent animal data suggest that reduced lipoic acid (LA) prevents oxidative inhibition of the nitrate bioactivating enzyme, the mitochondrial aldehyde dehydrogenase (ALDH-2), and that pentaerythritol tetranitrate (PETN) does not induce nitrate tolerance because of its intrinsic antioxidative properties, thereby preserving ALDH-2 activity. We sought to determine whether ALDH-2 activity in circulating white blood cells (WBCs) can be used to monitor nitrate tolerance and whether LA can prevent nitroglycerin tachyphylaxis in humans. Eight healthy male volunteers received, in randomized order, a single dose of glyceryl trinitrate (GTN; 0.8 mg), PETN (80 mg), or GTN plus LA (600 mg) orally. GTN (30 min) and PETN (120 min) administration lead to a comparable dilation of the brachial artery (15 +/- 1%). In contrast to PETN, acute GTN treatment resulted in a 60% decrease in WBC ALDH-2 activity (high-performance liquid chromatography), 30% reduction of nitrate bioactivation, and 25% decrease in serum antioxidant capacity (fluorescence assay), which all were prevented by pretreatment with LA. Mechanistic studies in rats identified oxidative stress, ALDH-2 inactivation, and vascular dysfunction as common features in acute and chronic nitrate tolerance. Treatment with GTN, but not PETN, acutely inhibits ALDH-2 activity and nitrate bioactivation in healthy volunteers. These effects were prevented by LA pretreatment, emphasizing the role of oxidative stress-triggered ALDH-2 dysfunction. Assessment of WBC ALDH-2 activity could be used as an easily accessible marker for the detection of nitroglycerin-induced tachyphylaxis in humans and may be of high clinical interest because recent data suggest that ALDH-2 activity correlates with protection from ischemic heart damage in infarct models.