Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis may affect patients after transcatheter aortic valve replacement (TAVR). OBJECTIVES: The purpose of this study was to provide detailed information on incidence rates, types of microorganisms, and outcomes of infective endocarditis after TAVR. METHODS: Between February 2011 and July 2018, consecutive patients from the SwissTAVI Registry were eligible. Infective endocarditis was classified into early (peri-procedural [<100 days] and delayed-early [100 days to 1 year]) and late (>1 year) endocarditis. Clinical events were adjudicated according to the Valve Academic Research Consortium-2 endpoint definitions. RESULTS: During the observational period, 7,203 patients underwent TAVR at 15 hospitals in Switzerland. During follow-up of 14,832 patient-years, endocarditis occurred in 149 patients. The incidence for peri-procedural, delayed-early, and late endocarditis after TAVR was 2.59, 0.71, and 0.40 events per 100 person-years, respectively. Among patients with early endocarditis, Enterococcus species were the most frequently isolated microorganisms (30.1%). Among those with peri-procedural endocarditis, 47.9% of patients had a pathogen that was not susceptible to the peri-procedural antibiotic prophylaxis. Younger age (subhazard ratio [SHR]: 0.969; 95% confidence interval [CI]: 0.944 to 0.994), male sex (SHR: 1.989; 95% CI: 1.403 to 2.818), lack of pre-dilatation (SHR: 1.485; 95% CI: 1.065 to 2.069), and treatment in a catheterization laboratory as opposed to hybrid operating room (SHR: 1.648; 95% CI: 1.187 to 2.287) were independently associated with endocarditis. In a case-control matched analysis, patients with endocarditis were at increased risk of mortality (hazard ratio: 6.55; 95% CI: 4.44 to 9.67) and stroke (hazard ratio: 4.03; 95% CI: 1.54 to 10.52). CONCLUSIONS: Infective endocarditis after TAVR most frequently occurs during the early period, is commonly caused by Enterococcus species, and results in considerable risks of mortality and stroke. (NCT01368250).

Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction.

IMPORTANCE: Whether sex-specific chest pain characteristics (CPCs) would allow physicians in the emergency department to differentiate women with acute myocardial infarction (AMI) from women with other causes of acute chest pain more accurately remains unknown. OBJECTIVE To improve the management of suspected AMI in women by exploring sex-specific CPCs. DESIGN, SETTING, AND PARTICIPANTS: From April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients (796 women and 1679 men) presenting with acute chest pain to 9 emergency departments in a prospective multicenter study. The final diagnosis of AMI was adjudicated by 2 independent cardiologists. INTERVENTIONS: Treatment of AMI in the emergency department. MAIN OUTCOMES AND MEASURES: Sex-specific diagnostic performance of 34 predefined and uniformly recorded CPCs in the early diagnosis of AMI. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 143 women (18.0%) and 369 men (22.0%). Although most CPCs were reported with similar frequency in women and men, several CPCs were reported more frequently in women (P < .05). The accuracy of most CPCs in the diagnosis of AMI was low in women and men, with likelihood ratios close to 1. Thirty-one of 34 CPCs (91.2%) showed similar likelihood ratios for the diagnosis of AMI in women and men, and only 3 CPCs (8.8%) seemed to have a sex-specific diagnostic performance with P < .05 for interaction. These CPCs were related to pain duration (2-30 and >30 minutes) and dynamics (decreasing pain intensity). However, because their likelihood ratios were close to 1, the 3 CPCs did not seem clinically helpful. Similar results were obtained when examining combinations of CPCs (all interactions, P ≥ .05). CONCLUSIONS AND RELEVANCE: Differences in the sex-specific diagnostic performance of CPCs are small and do not seem to support the use of women-specific CPCs in the early diagnosis of AMI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00470587.

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays.

AIMS: Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. METHODS AND RESULTS: In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. CONCLUSION: High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation values.

Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction.

BACKGROUND: Current guidelines require a change (rise and/or fall) in levels of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI). It is unknown whether absolute or relative changes provide higher accuracy when using high-sensitivity cTnI assays. METHODS: In a prospective international multicentre study, we assessed the diagnostic accuracy of early absolute and relative changes in cTnI measured with two novel pre-commercial high-sensitivity assays (Siemens and Beckman Coulter) in 943 unselected patients presenting to the ED with suspected AMI. The final diagnosis of AMI was adjudicated using all available data including serial hs-cTnT levels by two independent cardiologists. RESULTS: The diagnostic accuracy of absolute changes in the diagnosis of AMI as quantified by the area under the receiver operating characteristics curve (AUC) was very high (e.g. at 2 h, Siemens high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96; Beckman Coulter high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96) and superior to relative changes at all time points (p < 0.001). The results were consistent in clinically important subgroups. Direct comparison of the absolute changes in the two high-sensitivity cTnI assays showed similar accuracy. When combined with the baseline cTnI levels, the difference between absolute and relative changes became much smaller and remained statistically significant only for the Siemens assay. CONCLUSIONS: As single variables early absolute changes in high-sensitivity cTnI levels have significantly higher diagnostic accuracy than relative changes. When combined with the baseline cTn level, reflecting clinical practice, both absolute and relative changes provided very high accuracy with much smaller differences between both approaches.

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.

BACKGROUND: Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. METHODS: In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. CONCLUSIONS: Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI.

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin.

BACKGROUND: We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). METHODS AND RESULTS: In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs-cTnT levels, 21% had an adjudicated diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs-cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV) 98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5% of patients at presentation. The NPV was similar with the three hs-cTnI assays: among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was 98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter), the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to 13.9%. CONCLUSIONS: Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays.

Consideration of high-sensitivity troponin values below the 99th percentile at presentation: does it improve diagnostic accuracy?

BACKGROUND: The introduction of high-sensitivity cardiac troponin (hs-cTn) assays allows the assessment of clinical decision values below the 99th percentile. METHODS: Final diagnosis and one-year mortality were adjudicated in a multicenter, prospective cohort of 1181 patients presenting with acute chest pain to the emergency department. Hs-cTnT (Roche) and cTnI-ultra (Siemens) were measured in a blinded fashion. RESULTS: At presentation hs-cTnT and cTnI-ultra were below the limit of blank (LOB) in 201 (17%) and 549 (47%) patients, below the 75th percentile in 379 (32%) and 623 (53%) patients, below the 95th percentile in 603 (51%) and 808 (68%), and below the 99th percentile in 748 (63%) and 913 (77%), respectively. Sensitivities for the diagnosis of AMI were 100.0% and 96.8% respectively for hs-cTnT and cTnI-ultra (LOB as cut-off value), 99.5% and 96.2% (75th percentile), 96.8% and 93.0% (95th percentile), and 94.1% and 88.1% (99th percentile). The proportion of patients correctly classified as having or not AMI increased from 32.9% (LOB as cut-off value) to 47.8% (75th percentile), 65.9% (95th percentile) and 77.3% (99th percentile) for hs-cTnT and from 61.2% to 67.3%, 81.9% and 89.3% respectively for cTnI-ultra. At 1 year, all-cause mortality was very low and similar for patients below all of these cut-off levels (between 0.7% and 1.5%, p=0.748 for all-groups comparison). CONCLUSION: cTn should be considered as a continuous variable. Decision values below the 99th percentile (e.g. the 75th percentile) are associated with a very high NPV for the diagnosis of AMI, but have a lower accuracy than the 99th percentile.

Normal presenting levels of high-sensitivity troponin and myocardial infarction.

OBJECTIVE: To analyse whether levels of high-sensitivity cardiac troponin (hs-cTn) below their respective 99th percentile can be used as a single parameter to rule out acute myocardial infarction (AMI) at presentation. DESIGN: Prospective, multicentre study. MAIN OUTCOME MEASURES: We measured hs-cTn using four different methods (hs-cTnT Roche, hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting to the emergency department with acute chest pain. Two independent cardiologists adjudicated the final diagnosis. Patients were followed for death or AMI during a mean period of 24 months. RESULTS: Among 2072 consecutive patients with hs-cTnT measurements available, 21.4% had an adjudicated diagnosis of AMI (sensitivity 89.6%, 95% CI 86.4% to 92.3%, negative predictive value (NPV): 96.5%, 95% CI 95.4% to 97.4%). Among 1180 consecutive patients with hs-cTnI Siemens measurements available, 20.0% had AMI (sensitivity 94.1%, 95% CI 90.3% to 96.7%, NPV: 98.0%, 95% CI: 96.6% to 98.9%). Among 1151 consecutive patients with hs-cTnI Beckman Coulter measurements available, 19.7% had AMI (sensitivity 92.1%, 95% CI 87.8% to 95.2%, NPV: 97.5%, 95% CI 96.0% to 98.5%). Among 1567 consecutive patients with hs-cTnI Abbott measurements available, 20.0% had AMI (sensitivity 77.2%, 95% CI 72.1% to 81.7%, NPV: 94.3%, 95% CI 92.8% to 95.5%). CONCLUSIONS: Normal hs-cTn levels at presentation should not be used as a single parameter to rule out AMI as 6%-23% of adjudicated AMI cases had normal levels of hs-cTn levels at presentation. Our data highlight the lack of standardisation among hs-cTnI assays resulting in substantial differences in sensitivity and NPV at the 99th percentile.

Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays.

BACKGROUND: It is unknown whether unstable angina (UA) results in previously nondetectable low-level myocardial necrosis. We compared the pattern of myocardial necrosis between patients with UA, acute myocardial infarction (AMI), and noncardiac chest pain (NCCP) using 3 high-sensitive cardiac troponin (hs-cTn) assays. METHODS: In a multicenter study, we enrolled 842 unselected patients with acute chest pain in the emergency department. Roche hs-cTnT, Beckman Coulter hs-cTnI, and Siemens hs-cTnI were determined in a blinded fashion at presentation and after 1, 2, 3, and 6 hours. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: A change in hs-cTn of ≥2 ng/L within the first hour after presentation as assessed with Roche hs-cTnT, Beckman Coulter hs-cTnI, and Siemens hs-cTnI was observed in 26%, 31%, and 32% of patients with UA (n = 115) compared with 91%, 92%, and 96% in patients with AMI (n = 120) and 12%, 23%, and 16% in patients with NCCP (n = 415; P < .001 for all comparisons between UA and AMI, P > .05 for all comparisons between UA and NCCP). In patients with UA, such a 1-hour change in hs-cTn of ≥2 ng/L was associated with an increased risk of death or AMI during the 30-day follow-up (P = .003, .03, .03) and 2-year follow-up (P < .001, .002, and .006). CONCLUSIONS: In marked contrast to patients with AMI, most patients with UA do not exhibit relevant hs-cTn changes. The minority of UA with hs-cTn changes, however, has a significantly worse short- and long-term outcome.

Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea.

OBJECTIVES: Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). DESIGN: Prospective cohort study. SETTING: University hospital, emergency department. PATIENTS: 632 consecutive patients presenting with acute dyspnoea. MAIN OUTCOME MEASURES: MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. RESULTS: AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR proANP, p<0.001 and 4916 (2169-10285) versus 1177 (258-5166) pg/ml, p<0.001 for NT proBNP). Diagnostic accuracy in AF patients was similar for MR proANP (0.90, 95% CI 0.84 to 0.95) and NT proBNP (0.89, 95% CI 0.81 to 0.96). Optimal cut-off levels in AF patients were significantly higher compared with the optimal cut-off levels for patients in SR (MR proANP 240 vs 200 pmol/l; NT proBNP 2670 vs 1500 pg/ml respectively). After adjustment in multivariable Cox proportional hazard analysis, MR proANP strongly predicted one-year all-cause mortality (HR=1.13 (1.09-1.17), per 100 pmol/l increase, p<0.001). CONCLUSION: In AF patients, NT proBNP and MR proANP have similar diagnostic value for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays seem to improve the early diagnosis of acute myocardial infarction (AMI), but it is unknown how to best use them in clinical practice. Our objective was to develop and validate an algorithm for rapid rule-out and rule-in of AMI. METHODS: A prospective multicenter study enrolling 872 unselected patients with acute chest pain presenting to the emergency department. High-sensitivity cardiac troponin T (hs-cTnT) was measured in a blinded fashion at presentation and after 1 hour. The final diagnosis was adjudicated by 2 independent cardiologists. An hs-cTnT algorithm incorporating baseline values as well as absolute changes within the first hour was derived from 436 randomly selected patients and validated in the remaining 436 patients. The primary prognostic end point was death during 30 days of follow-up. RESULTS: Acute myocardial infarction was the final diagnosis in 17% of patients. After applying the hs-cTnT algorithm developed in the derivation cohort to the validation cohort, 259 patients (60%) could be classified as "rule-out," 76 patients (17%) as "rule-in," and 101 patients (23%) as in the "observational zone" within 1 hour. Overall, this resulted in a sensitivity and negative predictive value of 100% for rule-out, a specificity and positive predictive value of 97% and 84%, respectively, for rule-in, and a prevalence of AMI of 8% in the observational zone group. Cumulative 30-day survival was 99.8%, 98.6%, and 95.3% (P < .001) in patients classified as rule-out, observational zone, and rule-in, respectively. CONCLUSIONS: Using a simple algorithm incorporating hs-cTnT baseline values and absolute changes within the first hour allowed a safe rule-out as well as an accurate rule-in of AMI within 1 hour in 77% of unselected patients with acute chest pain. This novel strategy may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients.