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Background\ud \ud Infective endocarditis (IE) is an uncommon disease, but it is associated with high morbidity and mortality. The low incidence and varied clinical presentation make identification of these patients recently admitted to hospitals particularly challenging. The authors designed a prospective electronic health record screening tool (PEHRST) to identify inpatients with IE for a prospective case-control study designed to determine levels of association between oral hygiene and periodontal disease indexes and IE.\ud \ud \ud \ud Methods\ud \ud The authors used PEHRST to identify, soon after admission, patients hospitalized with IE based on the presence of any 2 of the 4 screening criteria: orders for blood culture or echocardiography and completed consultations from infectious diseases or cardiovascular medicine. They determined the utility of this tool by comparing the prospectively generated PEHRST list of potential inpatients with IE with a retrospective list of inpatients with IE discharged during the same 2-year period.\ud \ud \ud \ud Results\ud \ud Of the 74,345 patients admitted during the study period, PEHRST identified 11,944 (16%) with at least 2 of the 4 screening criteria. Retrospective claims data showed that 198 patients were discharged during this time period with an IE diagnosis, all of whom had been identified by PEHRST (sensitivity = 100%; 95% CI, 98.2% to 100%; specificity = 84%; 95% CI, 83.9% to 84.4%). An analysis of the timing of the 4 screening criteria indicated that the median days were all within 24 hours of admission.\ud \ud \ud \ud Conclusions\ud \ud PEHRST made possible the identification of rare patients with IE soon after hospital admission with high sensitivity, allowing the parent study to achieve sufficient enrollment of cases for the primary outcome measure.

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Background:\ud \ud Antibiotic prophylaxis (AP) before invasive dental procedures (IDP) is recommended to prevent infective endocarditis (IE) in those at high-IE-risk but there are sparse data supporting a link between IDP and IE or AP efficacy in IE-prevention.\ud \ud Objectives:\ud \ud To investigate any association between IDP and IE, and AP effectiveness in reducing this.\ud \ud Methods:\ud \ud We performed a case-crossover analysis and cohort study of the association between IDP and IE, and AP efficacy, in 7,951,972 US subjects with employer-provided Commercial/Medicare-Supplemental cover.\ud \ud Results:\ud \ud Time course studies showed that IE was most likely to occur within 4-weeks of an IDP. For those at high-IE-risk, case-crossover analysis demonstrated a significant temporal association between IE and IDP in the preceding 4-weeks (OR 2.00, 95%CI 1.59-2.52, p=0.002). This relationship was strongest for dental extractions (OR 11.08, 95%CI 7.34-16.74, p

Aims Shock is among the most dreaded and common complications of type A acute aortic dissection (TAAAD). However, clinical correlates, management, and short- and long-term outcomes of TAAAD patients presenting with shock in real-world clinical practice are not known. Methods and Results We evaluated 2,704 patients with TAAAD enrolled in the International Registry of Acute Aortic Dissection between January 1, 1996, and August 18, 2012. On admission, 407 (15.1%) TAAAD patients presented with shock. Most in-hospital complications (coma, myocardial or mesenteric ischemia or infarction, and cardiac tamponade) were more frequent in shock patients. In-hospital mortality was significantly higher in TAAAD patients with than without shock (30.2% vs 23.9%, P =.007), regardless of surgical or medical treatment. Most shock patients underwent surgical repair, with medically managed patients demonstrating older age and more complications at presentation. Estimates using Kaplan-Meier survival analysis indicated that most (89%) TAAAD patients with shock discharged alive from the hospital survived 5years, a rate similar to that of TAAAD patients without shock (82%, P =.609). Conclusions Shock occurred in 1 of 7 TAAAD patients and was associated with higher rates of in-hospital adverse events and mortality. However, TAAAD survivors with or without shock showed similar long-term mortality. Successful early and aggressive management of shock in TAAAD patients has the potential for improving long-term survival in this patient population.

Background— The outcome of patients with acute type B aortic dissection (ABAD) is strongly related to their clinical presentation. The purpose of this study was to investigate predictors for mortality among patients presenting with ABAD and to create a predictive model to estimate individual risk of in-hospital mortality using the International Registry of Acute Aortic Dissection (IRAD). Methods and Results— All patients with ABAD enrolled in IRAD between 1996 and 2013 were included for analysis. Multivariable logistic regression analysis was used to investigate predictors of in-hospital mortality. Significant risk factors for in-hospital death were used to develop a prediction model. A total of 1034 patients with ABAD were included for analysis (673 men; mean age, 63.5±14.0 years), with an overall in-hospital mortality of 10.6%. In multivariable analysis, the following variables at admission were independently associated with increased in-hospital mortality: increasing age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00–1.06; P =0.044), hypotension/shock (OR, 6.43; 95% CI, 2.88–18.98; P =0.001), periaortic hematoma (OR, 3.06; 95% CI, 1.38–6.78; P =0.006), descending diameter ≥5.5 cm (OR, 6.04; 95% CI, 2.87–12.73; P P P =0.001), and limb ischemia (OR, 3.02; 95% CI, 1.05–8.68; P =0.040). Based on these multivariable results, a reliable and simple bedside risk prediction tool was developed. Conclusions— We present a simple prediction model using variables that are independently associated with in-hospital mortality in patients with ABAD. Although it needs to be validated in an independent population, this model could be used to assist physicians in their choice of management and for informing patients and their families.

Background Acute aortic dissection associated with cocaine use is rare and has been reported predominantly as single cases or in small patient cohorts.Methods Our study analyzed 3584 patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2012. We divided the population on the basis of documented cocaine use (C+) versus noncocaine use (C-) and further stratified the cohorts into type A (33 C+/2332, 1.4%) and type B (30 C+/1252, 2.4%) dissection.Results C+ patients presented at a younger age and were more likely to be male and black. Type B dissections were more common among C+ patients than in C- patients. Cocaine-related acute aortic dissection was reported more often at US sites than at European sites (86.4%, 51/63 vs 13.6%, 8/63; P

Background: The classification of aortic dissection into acute (30 days). Overall survival was progressively lower through the 4 time periods. Conclusions: This IRAD classification system can provide clinicians with a more robust method of characterizing survival after aortic dissection over time than previous methods. This system will be useful for treating patients, counseling patients and families, and studying new diagnostic and treatment methods.

In-hospital mortality following Type A acute aortic dissection (TAAAD) repair was 23.9% in a 2007 International Registry of Acute Aortic Dissection (IRAD) report. Recent publications have described surgical mortality as low as 12.2%. This study evaluates the fitness of a previously published risk

Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.

Few data exist on race-related differences in acute aortic dissection patients.We evaluated black (n = 189, 14%) or white (n = 1165, 86%) patients (mean age 62.8 ± 15.3 years; 36.4% women) enrolled in 13 US centers participating in the International Registry of Acute Aortic Dissection. We excluded patients of other racial descent.Type B acute aortic dissection was more frequent in the black cohort (52.4% vs 39.3%, P = .001). Black patients were younger (mean age 54.6 ± 12.8 years vs 64.2 ± 15.2 years, P.001) and more likely to have a history of cocaine abuse (12% vs 1.6%, P.001), hypertension (89.7% vs 73.9%, P .001), and diabetes (13.2% vs 6.4%, P = .001). Conversely, they were less likely to have bicuspid aortic valve (1.8% vs 5.8%, P = .029), iatrogenic dissection (0.5% vs 4.5%, P = .010), and prior aortic dissection repair (7.7% vs 12.8%, P = .047). Presenting features were similar except for more abdominal pain (44.6% vs 30.6%, P.001) and left ventricular hypertrophy on echocardiogram (44.2% vs 20.1%, P .001) in blacks. Management was similar. Hypotension/shock/tamponade was less common (7.6% vs 20.1%, P.001), whereas acute kidney failure was more common (41.0% vs 21.7%, P.001) in blacks. Mortality was similar in-hospital (14.3% vs 19.1%, P = .110, odds ratio 0.704, 95% confidence interval 0.457-1.085) and at 3 years postdischarge, as evaluated by Kaplan-Meier survival analysis (22.0% vs 14.3%, P = .224, SE = 0.062 and 0.018).Our study shows differences in type, etiology, and presentation of blacks and whites with acute aortic dissection, yet similar mortality for these cohorts.

Background Acute type A aortic dissection (AAD) remains a highly lethal entity for which emergent surgical correction is standard care. Prior studies have identified specific clinical findings as being predictive of outcome. The prognostic significance of specific findings on imaging studies is less well described. We sought to identify the prognostic value of transesophageal echocardiography (TEE) in medically and surgically treated patients with AAD. Methods We studied 522 AAD patients enrolled over 6 years in the International Registry of Acute Aortic Dissection who underwent TEE. Multivariate analysis identified independent associations of inhospital mortality, first using clinical variables (model 1), after which TEE data were added to build a final model (model 2). Results Inhospital mortality was 28.7%. Transesophageal echocardiographic evidences of pericardial effusion ( P = .04), tamponade ( P P = .02), and patent false lumen ( P = .08) were more frequent in nonsurvivors. Dilated ascending aorta ( P = .03), dissection localized to the ascending aorta ( P = .02), and thrombosed false lumen ( P = .08) were less common in nonsurvivors. Model 1 identified age ≥70 years, any pulse deficit, renal failure, and hypotension/shock as independent predictors of death. Model 2 identified dissection flap confined to ascending aorta (odds ratio 0.2, 95% CI 0.1-0.6) and complete thrombosis of false lumen (odds ratio 0.15, 95% CI 0.03-0.86) as protective. In the medically treated group, mortality was 31% for subjects with a partially or completely thrombosed false lumen versus 66% in the presence of a patent false lumen. Conclusions Transesophageal echocardiography provides prognostic information in AAD beyond that provided by clinical risk variables.

Background Diagnosis, treatment, and outcomes of acute aortic dissection (AAS) are changing. Objectives This study examined 17-year trends in the presentation, diagnosis, and hospital outcomes of AAD from the International Registry of Acute Aortic Dissection (IRAD). Methods Data from 4,428 patients enrolled at 28 IRAD centers between December 26, 1995, and February 6, 2013, were analyzed. Patients were divided according to enrollment date into 6 equal groups and by AAD type: A (n = 2,952) or B (n = 1,476). Results There was no change in the presenting complaints of severe or worst-ever pain for type A and type B AAD (93% and 94%, respectively), nor in the incidence of chest pain (83% and 71%, respectively). Use of computed tomography (CT) for diagnosis of type A increased from 46% to 73% (p < 0.001). Surgical management for type A increased from 79% to 90% (p < 0.001). Endovascular management of type B increased from 7% to 31% (p < 0.001). Type A in-hospital mortality decreased significantly (31% to 22%; p < 0.001), as surgical mortality (25% to 18%; p = 0.003). There was no significant trend in in-hospital mortality in type B (from 12% to 14%). Conclusions Presenting symptoms and physical findings of AAD have not changed significantly. Use of chest CT increased for type A. More patients in both groups were managed with interventional procedures: surgery in type A and endovascular therapy in type B. A significant decrease in overall in-hospital mortality was seen for type A but not for type B.

We have characterized the age-related changes of contractility and beta-adrenoceptor function in isolated cardiac myocytes from guinea-pigs. We used either adult animals from 2 to 14 weeks of age, where body weight increases linearly with age, or senescent ones aged between 53-65 weeks. There was some indication of a decrease in contractility in maximum Ca2+ with age, with significant differences between a young (or = 4 weeks, weight400 g) and aged (or = 8 weeks, weight600 g) group in contraction amplitude expressed as percentage shortening (but not when expressed as micron change in length) or contraction and relaxation velocities. This decline was continued into senescence, and ANOVA showed a significant difference between the three groups for contraction amplitude (percentage shortening, 12.2 +/- 0.9%, young, n = 31; 9.5 +/- 0.6%, n = 28 aged; 6.7 +/- 0.8%, n = 6, senescent; P = 0.005), and contraction or relaxation velocities (P0.001). There was a more pronounced decline in maximum response to isoproterenol with age. ANOVA for the maximum isoproterenol response for the three divisions showed significant differences for percentage shortening (11.8 +/- 0.7%, n = 30, young; 7.9 +/- 0.5%, n-28, aged and 5.5 +/- 1.1%, n = 6, senescent; P0.001), velocities of contraction (P0.001) and relaxation (P0.001), and normalized velocities of contraction (P0.001) and relaxation (P0.01) at maximum isoproterenol, as well as in ISO EC50 (P0.001) and isoproterenol/Ca2+ ratio (P0.02). A general decrease in contractility of the myocyte occurs as the animal ages, with maximum contraction amplitude being reduced and velocity of contraction and relaxation slowed. The effect was more pronounced for beta-adrenoceptor stimulation than for high Ca2+, suggesting a specific lesion in the adenylate cyclase related pathway. Much of the change occurred between the young adult (or = 4 weeks) and the aged adult (or = 8 weeks), although the trend was continued in senescent animals (52 weeks).

Background— In patients with acute type B aortic dissection, presence of recurrent or refractory pain and/or refractory hypertension on medical therapy is sometimes used as an indication for invasive treatment. The International Registry of Acute Aortic Dissection (IRAD) was used to investigate the impact of refractory pain and/or refractory hypertension on the outcomes of acute type B aortic dissection. Methods and Results— Three hundred sixty-five patients affected by uncomplicated acute type B aortic dissection, enrolled in IRAD from 1996 to 2004, were categorized according to risk profile into 2 groups. Patients with recurrent and/or refractory pain or refractory hypertension (group I; n=69) and patients without clinical complications at presentation (group II; n=296) were compared. “High-risk” patients with classic complications were excluded from this analysis. The overall in-hospital mortality was 6.5% and was increased in group I compared with group II (17.4% versus 4.0%; P =0.0003). The in-hospital mortality after medical management was significantly increased in group I compared with group II (35.6% versus 1.5%; P =0.0003). Mortality rates after surgical (20% versus 28%; P =0.74) or endovascular management (3.7% versus 9.1%; P =0.50) did not differ significantly between group I and group II, respectively. A multivariable logistic regression model confirmed that recurrent and/or refractory pain or refractory hypertension was a predictor of in-hospital mortality (odds ratio, 3.31; 95% confidence interval, 1.04 to 10.45; P =0.041). Conclusions— Recurrent pain and refractory hypertension appeared as clinical signs associated with increased in-hospital mortality, particularly when managed medically. These observations suggest that aortic intervention, such as via an endovascular approach, may be indicated in this intermediate-risk group.

To evaluate the clinical characteristics, risk factors, and outcomes of hypotension in unselected patients who had acute aortic dissection (AAD), we studied 1,073 such patients who were enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2001. Hypotension was noted in 313 patients (29.2%) who had AAD (46.0% on admission). Multivariate logistic regression identified ageor=70 years (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4 to 2.9), type A dissection (referent type B AAD; OR 2.1, 95% CI 1.4 to 3.2), neurologic deficit (OR 3.8, 95% CI 2.2 to 6.6), syncope (OR 2.9, 95% CI 1.8 to 4.7), aortic regurgitation requiring valve surgery (OR 1.9, 95% CI 1.1 to 3.3), cardiac tamponade (OR 5.1, 95% CI 3.0 to 8.8), and new Q-wave or ST-segment deviation on an electrocardiogram (OR 1.6, 95% CI 1.1 to 2.4) as independent associations of hypotension (c statistic 0.78). Hospital complications (neurologic deficits 22.7% vs 12.0%, altered mental status 26.1% vs 4.4%, myocardial ischemia 14.6% vs 6.9%, mesenteric ischemia 6.9% vs 2.6%, or limb ischemia 14.6% vs 6.9%, and death 55.0% vs 10.3%) occurred more frequently in patients who had hypotension than in those who did not (p0.001 for all comparisons). We concluded that hypotension that occurred in25% of patients who had AAD was associated with a much higher rate of in-hospital adverse events. Our study also identified factors associated with hypotension in patients who had AAD.

A decline in contractility in myocytes from ageing guinea-pig hearts was demonstrated, which is more pronounced for maximum beta-adrenoceptor-stimulated activity than contraction in high Ca2+. In this study the role of the inhibitory G-proteins (Gi) in this process was investigated. Comparisons were made between young (Y,400 g,4 weeks), adult (A.600 g,8 weeks) and senescent guinea pigs (S, 58-65 weeks, 1136 +/- 30 g). Gi alpha activity, detected by pertussis toxin-catalysed ADP ribosylation, was significantly increased in senescent compared to young animals, but immunodetectable levels of Gi alpha were unchanged, beta-adrenoceptor number was decreased by 27% in senescent compared with young animals (P0.002). Pertussis toxin treatment increased the maximum response to isoproterenol in contacting myocytes so that there was no longer any significant decline with age. Maximum contraction amplitudes (sarcomere length change, micron) with isoproterenol before pertussis toxin were 0.144 +/- 0.011 (Y, n = 22 animals), 0.104 +/- 0.009 (A. 18) and 0.098 +/- 0.009 (S. 14), P0.01 by analysis of variance (ANOVA). Following toxin treatment amplitudes were 0.140 +/- 0.012 (Y. 12), 0.117 +/- 0.010 (A. 10) and 0.117 +/- 0.018 (S. 8), P = N.S. Pertussis toxin treatment also reversed the effects of ageing on contraction and relaxation velocity in isoproterenol. In contrast, the effect of age on contraction amplitude or velocity in maximum Ca2+ was more pronounced after toxin treatment. The EC50 value for isoproterenol increased with age: pertussis treatment decreased the EC50 in each group, but the effect was especially pronounced for senescent animals. There was no significant difference in the concentration-response curves for the negative inotropic effect of adenosine (in the presence of isoprotenerol) between the three age groups before toxin treatment. All effects of adenosine were abolished after pertussis exposure. We conclude that increased Gi alpha activity is likely to contribute to the decreased response to isoproterenol, but not to high Ca2+, in myocytes from ageing guinea-pigs.