Optimal cutoff-value of Siemens cardiac troponin I assay in patients with kidney disease for the early diagnosis of acute myocardial infarction

Purpose: The recent introduction of more sensitive cardiac troponin (cTn) assays improved the early diagnosis of acute myocardial infarction (AMI). However, its diagnostic utility has never been tested in patients with kidney disease (KD), who are known to have elevated levels of cTn already in the absence of AMI, which may lead to a lower diagnostic value of more sensitive cTn in this high-risk subgroup. Methods: We conducted an international multicenter study to examine the diagnostic accuracy of the Siemens cTnI Ultra assay in 1997 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, of whom 343 (17%) were determined to have KD (MDRD GFR <60ml/min/1.73m2) and to derive the optimal cutoff-value for the diagnosis of AMI in patients with KD. The diagnostic accuracy was further compared to a conventional cTn assay (Roche Troponin T fourth generation). The final diagnosis was adjudicated by two independent cardiologists based on hs-cTnT. Results: AMI was the final diagnosis in 35% (n=120) of all KD-patients as compared to 18% in patients with normal kidney function (p<0.001). Among KD-patients with other diagnoses than AMI, baseline hs-cTnI-levels were elevated above the 99thpercentile in 20%, In patients with KD the diagnostic accuracy at presentation, quantified by the area under the receiver-operator-characteristic curve (AUC), was significantly greater for Siemens cTnI as compared to the standard cTnT assay (AUC for cTnI, 0.88 vs. AUC for the standard assay, 0.82, p=0.013). In patients presenting within three hours after the onset of chest pain, the superiority of Siemens cTnI over conventional cTnT was even more pronounced (AUC 0.86 vs. 0.72, p=0.005). In KD, the optimal hs-cTnI cutoff derived from the ROC curve was 46 ng/l compared to 19 ng/l in patients with normal kidney function (standard 99th percentile 40 ng/l, provided by the manufacturer). Conclusions: The Siemens cTnI Ultra assay has a very high diagnostic accuracy also in KD-patients and is superior to a conventional cTnT-assay. Mild cTnI elevations are common in non-AMI patients. The optimal cutoff-level in KD-patients seems to be around the 99th percentile of a standard population, whereas the optimal cutoff-level in patients with normal kidney function tends to be only half of the suggested cutoff-value. ClinicalTrials.gov number, NCT0047058

Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion

BACKGROUND: Treatment to restore sinus rhythm among patients with atrial fibrillation (AF) has limited long-term success rates. Gene expression profiling may provide new insights into AF pathophysiology. OBJECTIVE: To identify biomarkers and improve our understanding of AF pathophysiology by comparing whole blood gene expression before and after electrical cardioversion (ECV). METHODS: In 46 patients with persistent AF that underwent ECV, whole blood samples were collected 1-2 hours before and 4 to 6 weeks after successful cardioversion. The paired samples were sent for microarray and plasma biomarker comparison. RESULTS: Of 13,942 genes tested, expression of SLC25A20 and PDK4 had the strongest associations with AF. Post-cardioversion, SLC25A20 and PDK4 expression decreased by 0.8 (CI 0.7-0.8, p = 2.0x10-6) and 0.7 (CI 0.6-0.8, p = 3.0x10-5) fold respectively. Median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations decreased from 127.7 pg/mL to 44.9 pg/mL (p = 2.3x10-13) after cardioversion. AF discrimination models combining NT-proBNP and gene expression (NT-proBNP + SLC25A20 area under the curve = 0.88, NT-proBNP + PDK4 AUC = 0.86) had greater discriminative capacity as compared with NT-proBNP alone (AUC = 0.82). Moreover, a model including NT-proBNP, SLC25A20 and PDK4 significantly improved AF discrimination as compared with other models (AUC = 0.87, Net Reclassification Index 5.8x10-3). We validated the association between SLC25A20 and PDK4 with AF in an independent sample of 17 patients. CONCLUSION: This study demonstrates that SLC25A20, PDK4, and NT-proBNP have incremental utility as biomarkers discriminating AF from sinus rhythm. Elevated SLC25A20 and PDK4 expression during AF indicates an important role for energy metabolism in AF

Effects of Sinus Rhythm Maintenance on Left Heart Function After Electrical Cardioversion of Atrial Fibrillation: Implications for Tachycardia-Induced Cardiomyopathy

BACKGROUND: The role of tachycardia-induced cardiomyopathy vs tachycardia-related short diastolic filling period and reduced atrial contraction in decline of left ventricular ejection fraction (LVEF) in atrial fibrillation (AF) is uncertain. We aimed to characterize left heart changes over time in patients with AF who undergo electrical cardioversion (ECV). METHODS: Consecutive AF patients who were to undergo ECV were enrolled. Patients with unstable or acute heart failure, severe valvular diseases, recent open-heart surgery, major disorders, or an unsuccessful ECV were excluded. Transthoracic echocardiography, including 3-dimensional left atrial and ventricular volume acquisitions, was performed 1-2 hours before and after ECV, and 4-6 weeks later. RESULTS: In 73 patients (77% male, 66 +/- 11 years), ECV resulted in an immediate increase in LVEF (from 43 [interquartile range (IQR), 33-50%] to 48 [IQR, 40-53%]; P > 0.0001). Four to 6 weeks after ECV, ejection fraction increased further in patients who remained in sinus rhythm (SR) (n = 55) to 55 (IQR, 44-62)%; P > 0.001. In patients with AF relapse, LVEF returned to values comparable to pre-ECV (n = 18) (44 [IQR, 32-51]%; P = 0.03). The atrial emptying fraction did not significantly change immediately after ECV (n = 69; from 20 [IQR, 13-25]% to 20 [IQR, 15-28]%; P = 0.14). Only patients who remained in SR showed an increase in atrial emptying fraction after 4-6 weeks (n = 51; to 37 [IQR, 26-48]%; P > 0.0001 vs post-ECV). CONCLUSIONS: Immediate improvement in LVEF after ECV explains approximately 50% of total LVEF increase over time. However, in SR, LVEF, and atrial function continuously increase over 4-6 weeks after ECV. This might be attributable to recovery of tachycardia-induced cardiomyopathy