Jaffe, Allan S.

Background— Primary amyloidosis has a poor prognosis as a result of frequent cardiac involvement. We recently reported a high prevalence of intracardiac thrombus in cardiac amyloid patients at autopsy. However, neither the prevalence nor the effect of anticoagulation on intracardiac thrombus has been evaluated antemortem. Methods and Results— We studied all transthoracic and transesophageal echocardiograms of cardiac amyloid patients at the Mayo Clinic. The prevalence of intracardiac thrombosis, clinical and transthoracic/transesophageal echocardiographic risks for intracardiac thrombosis, and effect of anticoagulation were investigated. We identified 156 patients with cardiac amyloidosis who underwent transesophageal echocardiograms. Amyloidosis was the primary type (AL) in 80; other types occurred in 76 patients, including 56 with the wild transthyretin type, 17 with the mutant transthyretin type, and 3 with the secondary type. Fifth-eight intracardiac thrombi were identified in 42 patients (27%). AL amyloid had more frequent intracardiac thrombus than the other types (35% versus 18%; P =0.02), although the AL patients were younger and had less atrial fibrillation. Multivariate analysis showed that atrial fibrillation, poor left ventricular diastolic function, and lower left atrial appendage emptying velocity were independently associated with increased risk for intracardiac thrombosis, whereas anticoagulation was associated with a significantly decreased risk (odds ratio, 0.09; 95% CI, 0.01 to 0.51; P <0.006). Conclusions— Intracardiac thrombosis occurs frequently in cardiac amyloid patients, especially in the AL type and in those with atrial fibrillation. Risk for thrombosis increased if left ventricular diastolic dysfunction and atrial mechanical dysfunction were present. Anticoagulation therapy appears protective. Timely screening in high-risk patients may allow early detection of intracardiac thrombus. Anticoagulation should be carefully considered.

Abstract Background: Improvements in cardiac troponin (cTn) assays have increased the rapidity with which clinicians can identify patients with changing cTn concentrations (rise or fall) indicative of acute myocardial injury. The aim of the present study was to characterize a new, high-sensitivity cTnI (hs-cTnI) assay and examine whether increased sensitivity can result in still earlier detection of evolving injury. Methods: We determined the limit of detection, precision profiles, and preliminary estimates of the 99th percentile for the Beckman Coulter hs-cTnI assay in 125 healthy individuals (age &lt;55 years, 54% male). We compared AccuTnI® and hs-cTnI to assess whether change criteria for early concentration changes (i.e., ≥3SD for low concentrations and 20% difference for concentrations &gt;0.10 μg/L) were exceeded in the first 2 specimens (median time between specimens, 1 h; 25th–75th percentile, 1–3 h) from subjects with symptoms suggestive of cardiac ischemia (n = 290). Results: The limit of detection for the hs-cTnI assay was 2.06 ng/L, and the 20% CV and 10% CV concentrations were 2.95 and 8.66 ng/L, respectively. The preliminary 99th percentile estimates in lithium heparin, serum, and EDTA plasma were 9.20, 8.00, and 8.60 ng/L, respectively. In 108 patients with myocardial injury based on the peak AccuTnI concentration, applying the change criteria on the 2 earliest specimens identified 81% (95% CI 73%–88%) of patients using the hs-cTnI assay compared to 62% (53%–71%) using the AccuTnI assay (P &lt; 0.001). Conclusions: Although more extensive validation studies are required, this Beckman Coulter hs-cTnI assay appears to detect patients with evolving myocardial injury earlier.

Background— Myonecrosis after percutaneous coronary intervention (PCI) has been correlated with a worse prognosis, but controversy exists about the clinical significance and potential mechanisms for the association. The aim of this study was to evaluate the relative impact of preprocedural and postprocedural cardiac troponin T (cTnT) levels on survival rate after PCI. Methods and Results— We evaluated 5487 patients from the Mayo Clinic registry who required nonemergency PCI, and we examined the relationship between periprocedural cTnT levels, with the 99th percentile cutoff value used for normal (<0.01 ng/mL), and outcomes. The patients were divided into 3 groups: normal preprocedural and postprocedural cTnT levels (no myonecrosis), normal preprocedural but elevated postprocedural cTnT levels (PCI-related myonecrosis), and abnormal preprocedural cTnT. The 30-day death rates were 0.1%, 0.6%, and 2.3%, respectively, in the 3 groups. In a multivariable model, an abnormal pre-PCI cTnT level (hazard ratio 9.66 [2.30–40.57]; P =0.002), and PCI-related myonecrosis (4.71 [1.02–21.83]; P =0.048) were independent predictors of 30-day mortality. Over a median follow-up of 28 months, an abnormal pre-PCI cTnT level (hazard ratio 1.79 [1.35–2.39]; P <0.001) independently predicted death, but the occurrence of PCI-related myonecrosis did not. A postprocedural elevation in creatine kinase MB fraction was not an independent predictor of long-term risk of death (0.912 [0.70–1.19]; P =0.5). Conclusions— A preprocedural cTnT level >0.01 is a powerful independent predictor of prognosis after PCI and is of greater prognostic significance than the postprocedural biomarker levels. PCI-related myonecrosis occurs frequently and predicts short-term but not long-term risk of death.

Abstract Background: Sophisticated methods of cardiac imaging have the potential to revolutionize the care of patients with cardiovascular disease. The benefits of these state-of-the art imaging techniques can be enhanced by their use in combination with new cardiac biomarkers. This review addresses potentially useful interactions between imaging and biomarkers. Content: Areas were defined in which the combined use of novel imaging techniques and biomarkers would be most beneficial. This review addresses multiple cardiovascular conditions for which the useful aspects of imaging and biomarkers are likely to be positively synergistic, including acute and chronic ischemic heart disease, heart failure, myocarditis, hypertension, and atherosclerosis. Conclusions: The synergistic use of imaging techniques and biomarkers will enhance the investigation of many key issues and questions and will be an important resource in the future.

Abstract Background: We investigated whether higher concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs. Methods: NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs. Results: We observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95-fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations ≥100 ng/L than in patients taking any inhibitor who had NT-proBNP values &lt;100 ng/L (P &lt; 0.05). Patients taking coxibs (alone or in addition to tNSAIDs or glucocorticoids) with baseline NT-proBNP values ≥100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values &lt;100 ng/L (P &lt; 0.01). Patients who were taking 2 or more antiinflammatory drugs and had NT-proBNP values ≥100 ng/L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values &lt;100 ng/L (P &lt; 0.05). An NT-proBNP value &lt;100 ng/L was associated with negative predictive values of &gt;85% across all treatment groups. Conclusions: NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.