AUC

2014 Top Stories in Cardiology: Cardiac Imaging.

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In assembling the top stories of 2014 in the field of cardiac imaging, we have focused on the major modalities of noninvasive imaging—echocardiography, nuclear cardiology, cardiac magnetic resonance imaging (CMR), and cardiac computed tomographic (CCT) imaging.

Echocardiography

The management of patients with severe mitral regurgitation due to myxomatous degeneration of the valve, particularly if asymptomatic, remains vexing. Naji and colleagues1 reported on exercise echocardiographic and clinical data in almost 900 patients with myxomatous mitral regurgitation, the majority of whom were asymptomatic. Patients were followed for a composite outcome for an average of over 6 years. Significant predictors of adverse outcomes included percent of age-/sex-predicted metabolic equivalents, heart rate recovery, resting right ventricular systolic pressure, atrial fibrillation, and LV ejection fraction. The importance of this paper lies not only in the large population with long-term follow-up, but also with the incorporation of exercise parameters into the usual clinical data, which had not been done before in such a large population. In the absence of randomized trials addressing timing of mitral valve surgery for asymptomatic severe mitral regurgitation, which are unlikely to be performed, this type of observational data set will inform guidelines and practice patterns.

Nuclear Cardiology

Almost 10 years ago, the American College of Cardiology published the first of a series of papers on the appropriate use of medical testing, originally called “Appropriateness Criteria,” now referred to as “Appropriate Use Criteria” (AUC). The goal of these recommendations is to optimize the efficiency and value of cardiac testing, based as much as possible on the published literature but also incorporating critical expert opinion. Recommendations are grouped by common clinical indications, and are categorized as “appropriate,” “may be appropriate” (formerly “uncertain”), or “rarely appropriate” (formerly “inappropriate”). Studies categorized as rarely appropriate are generally thought to be low-yield, in low-risk populations as an example. While AUC documents have been published for all common cardiac imaging tests and also for disease states such as stable ischemic heart disease or heart failure, there exists almost no literature validating the AUC categories in a prospective way against clinical outcomes. In this important paper, Doukky and colleagues2 report on over 1500 outpatients who were clinically referred for SPECT myocardial perfusion imaging. The studies were classified based on the 2009 AUC for SPECT myocardial perfusion imaging into two categories as appropriate/uncertain or as inappropriate. Patients were followed for an average of over 2 years for adverse events. Among the studies categorized as being of appropriate/uncertain indication, the SPECT results showed the usual prognostic value, in that an abnormal study was associated with a higher risk for adverse events compared with a normal study. However, among the SPECT studies characterized as inappropriate, there was not demonstrable prognostic association. To some degree, this was a result of the very low event rate among those with inappropriate studies, in turn related to the very low prevalence of abnormal studies. Nonetheless, these data are the first to examine the AUC recommendations in terms of association with outcomes, and validate the recommendations of the AUC documents. The importance of this paper lies in the fact that, within the next few years, payors including CMS will be mandating incorporation of AUC into the stream of test-ordering behavior. Having well-validated criteria is a critical element in the widespread acceptance of this approach.

Cardiac MR Imaging

Several relatively small studies have suggested that the presence and/or extent of late gadolinium hyperenhancement (LGE) on CMR imaging in patients with hypertrophic cardiomyopathy is associated with the risk for adverse events or with markers of adverse events. In this largest study to date,3 the authors assembled almost 1300 patients with hypertrophic cardiomyopathy from several centers around the world who had CMR imaging and were followed for a median of over 3 years. There was a significant association between the extent of LGE and risk for sudden death events. Among patients without established risk factors for sudden death, the extent of LGE was associated with sudden death risk, and, among those without LGE, risk was very low. The importance of this data set is that it more clearly establishes the role of CMR imaging in the prediction of sudden death risk in patients with hypertrophic cardiomyopathy. For those in whom the ICD decision may be uncertain on the basis of the usual clinical risk factors, the presence or absence of a certain mass of LGE on CMR imaging can tip the scales one way or the other on that critical decision point. For patients without any of the established risk factors, the presence and extent of LGE may drive consideration for an ICD that might not otherwise have been entertained. This study population is much larger with longer follow-up than all previous studies, allowing much more statistical power in analysis.

Cardiac CT Imaging

The technology of cardiac CT angiography has evolved substantially over the last decade, and, while the focus of much of the literature has been to recapitulate and expand the application of this modality in the same way as invasive angiography has been done, more recently, increasing attention has been on the evaluation of “non-obstructive” coronary artery disease (CAD). This can be imaged more routinely with contemporary CT techniques. In this paper, Bittencourt and colleagues4 report on over 3000 patients who had CT angiography whose scans were evaluated for the presence and extent of obstructive as well as non-obstructive CAD, and who were followed for a median of over 3 years for the occurrence of cardiovascular death or nonfatal myocardial infarction. The expected relation of obstructive CAD to events was seen, but, of great interest, those patients with extensive non-obstructive CAD had a risk for events that was similar to that in patents with less extensive obstructive CAD. Non-obstructive plaque extent added incremental information to risk stratification. These data are important for advancing the possibility of incorporating information on extent of imaged plaque into risk assessments, which may, in the future, help guide treatment decisions, or decisions regarding intensity of risk-factor management.

Conclusions

While the mature imaging modalities of echocardiography and nuclear cardiology have long had published data sets involving thousands of patients with sophisticated statistical analyses, the studies cited above suggest that the more recently evolved modalities of cardiac MR and cardiac CT have also reached a similar point regarding the rigor of prognostic data sets and publications. As always, finer gradations of risk assessment and stratification do not necessarily translate into enhanced management for patients, and must be tested separately and not simply be assumed.

Age-Related Changes in Nanoparticle Albumin-Bound Paclitaxel Pharmacokinetics and Pharmacodynamics: Influence of Chronological Versus Functional Age

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Purpose. This study evaluated age-related changes in pharmacokinetic and pharmacodynamic parameters of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with metastatic breast cancer.

Methods. Forty patients received nab-paclitaxel (100 mg/m2 weekly for 3 weeks followed by a 1-week break) as first- or second-line chemotherapy. Blood samples were collected for analysis, and response was assessed every two cycles. Planned statistical analyses included linear regression to examine the relationship between age and pharmacokinetic variables (ln clearance [CL] and ln area under the curve [AUC]) and two-sided two-sample t tests to evaluate age differences in pharmacodynamic variables. The association between chemotherapy toxicity risk scores and pharmacokinetic and pharmacodynamic variables including grade ≥3 toxicity were examined post hoc.

Results. Of 40 patients enrolled, 39 (98%) were evaluable (mean age: 60 years; range: 30–81 years). A partial response was achieved in 31%, and 38% had stable disease. There was a borderline positive association between age and 24-hour ln AUC (slope = 0.011; SE = 0.006; p = .055). Grade 3 toxicity was experienced by 26% (8% hematologic, 18% nonhematologic). There were no differences in age based on the presence of grade 3 toxicity (p = .75), dose reductions (p = .38), or dose omissions (p = .15). A significant association was noted between chemotherapy toxicity risk score category and presence of grade 3 toxicity (toxicity rate by risk score category: low, 5 of 30 patients; medium, 3 of 6 patients; high, 2 of 3 patients; p = .041).

Conclusion. A borderline significant relationship exists between age and 24-hour AUC, but no differences were noted for pharmacodynamic variables (grade 3 toxicity, dose reductions, or dose omissions) based on age. There is an association between toxicity risk score and grade ≥3 chemotherapy toxicity and pharmacokinetic variables. The treatment is well tolerated across all age groups.

2014 Top Stories in Cardiology: Cardiac Imaging

Posted by

0


In assembling the top stories of 2014 in the field of cardiac imaging, we have focused on the major modalities of noninvasive imaging—echocardiography, nuclear cardiology, cardiac magnetic resonance imaging (CMR), and cardiac computed tomographic (CCT) imaging.

Echocardiography

The management of patients with severe mitral regurgitation due to myxomatous degeneration of the valve, particularly if asymptomatic, remains vexing. Naji and colleagues1 reported on exercise echocardiographic and clinical data in almost 900 patients with myxomatous mitral regurgitation, the majority of whom were asymptomatic. Patients were followed for a composite outcome for an average of over 6 years. Significant predictors of adverse outcomes included percent of age-/sex-predicted metabolic equivalents, heart rate recovery, resting right ventricular systolic pressure, atrial fibrillation, and LV ejection fraction. The importance of this paper lies not only in the large population with long-term follow-up, but also with the incorporation of exercise parameters into the usual clinical data, which had not been done before in such a large population. In the absence of randomized trials addressing timing of mitral valve surgery for asymptomatic severe mitral regurgitation, which are unlikely to be performed, this type of observational data set will inform guidelines and practice patterns.

Nuclear Cardiology

Almost 10 years ago, the American College of Cardiology published the first of a series of papers on the appropriate use of medical testing, originally called “Appropriateness Criteria,” now referred to as “Appropriate Use Criteria” (AUC). The goal of these recommendations is to optimize the efficiency and value of cardiac testing, based as much as possible on the published literature but also incorporating critical expert opinion. Recommendations are grouped by common clinical indications, and are categorized as “appropriate,” “may be appropriate” (formerly “uncertain”), or “rarely appropriate” (formerly “inappropriate”). Studies categorized as rarely appropriate are generally thought to be low-yield, in low-risk populations as an example. While AUC documents have been published for all common cardiac imaging tests and also for disease states such as stable ischemic heart disease or heart failure, there exists almost no literature validating the AUC categories in a prospective way against clinical outcomes. In this important paper, Doukky and colleagues2 report on over 1500 outpatients who were clinically referred for SPECT myocardial perfusion imaging. The studies were classified based on the 2009 AUC for SPECT myocardial perfusion imaging into two categories as appropriate/uncertain or as inappropriate. Patients were followed for an average of over 2 years for adverse events. Among the studies categorized as being of appropriate/uncertain indication, the SPECT results showed the usual prognostic value, in that an abnormal study was associated with a higher risk for adverse events compared with a normal study. However, among the SPECT studies characterized as inappropriate, there was not demonstrable prognostic association. To some degree, this was a result of the very low event rate among those with inappropriate studies, in turn related to the very low prevalence of abnormal studies. Nonetheless, these data are the first to examine the AUC recommendations in terms of association with outcomes, and validate the recommendations of the AUC documents. The importance of this paper lies in the fact that, within the next few years, payors including CMS will be mandating incorporation of AUC into the stream of test-ordering behavior. Having well-validated criteria is a critical element in the widespread acceptance of this approach.

Cardiac MR Imaging

Several relatively small studies have suggested that the presence and/or extent of late gadolinium hyperenhancement (LGE) on CMR imaging in patients with hypertrophic cardiomyopathy is associated with the risk for adverse events or with markers of adverse events. In this largest study to date,3 the authors assembled almost 1300 patients with hypertrophic cardiomyopathy from several centers around the world who had CMR imaging and were followed for a median of over 3 years. There was a significant association between the extent of LGE and risk for sudden death events. Among patients without established risk factors for sudden death, the extent of LGE was associated with sudden death risk, and, among those without LGE, risk was very low. The importance of this data set is that it more clearly establishes the role of CMR imaging in the prediction of sudden death risk in patients with hypertrophic cardiomyopathy. For those in whom the ICD decision may be uncertain on the basis of the usual clinical risk factors, the presence or absence of a certain mass of LGE on CMR imaging can tip the scales one way or the other on that critical decision point. For patients without any of the established risk factors, the presence and extent of LGE may drive consideration for an ICD that might not otherwise have been entertained. This study population is much larger with longer follow-up than all previous studies, allowing much more statistical power in analysis.

Cardiac CT Imaging

The technology of cardiac CT angiography has evolved substantially over the last decade, and, while the focus of much of the literature has been to recapitulate and expand the application of this modality in the same way as invasive angiography has been done, more recently, increasing attention has been on the evaluation of “non-obstructive” coronary artery disease (CAD). This can be imaged more routinely with contemporary CT techniques. In this paper, Bittencourt and colleagues4 report on over 3000 patients who had CT angiography whose scans were evaluated for the presence and extent of obstructive as well as non-obstructive CAD, and who were followed for a median of over 3 years for the occurrence of cardiovascular death or nonfatal myocardial infarction. The expected relation of obstructive CAD to events was seen, but, of great interest, those patients with extensive non-obstructive CAD had a risk for events that was similar to that in patents with less extensive obstructive CAD. Non-obstructive plaque extent added incremental information to risk stratification. These data are important for advancing the possibility of incorporating information on extent of imaged plaque into risk assessments, which may, in the future, help guide treatment decisions, or decisions regarding intensity of risk-factor management.

Conclusions

While the mature imaging modalities of echocardiography and nuclear cardiology have long had published data sets involving thousands of patients with sophisticated statistical analyses, the studies cited above suggest that the more recently evolved modalities of cardiac MR and cardiac CT have also reached a similar point regarding the rigor of prognostic data sets and publications. As always, finer gradations of risk assessment and stratification do not necessarily translate into enhanced management for patients, and must be tested separately and not simply be assumed.

Threshold-Based Insulin-Pump Interruption for Reduction of Hypoglycemia.

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BACKGROUND

The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia.

METHODS

We randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values.

RESULTS

A total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insulin-pump therapy (control group, 126 patients). The changes in glycated hemoglobin values were similar in the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group (980±1200 mg per deciliter [54.4±66.6 mmol per liter]×minutes vs. 1568±1995 mg per deciliter [87.0±110.7 mmol per liter]×minutes, P<0.001). Nocturnal hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group than in the control group (1.5±1.0 vs. 2.2±1.3 per patient-week, P<0.001). The percentages of nocturnal sensor glucose values of less than 50 mg per deciliter (2.8 mmol per liter), 50 to less than 60 mg per deciliter (3.3 mmol per liter), and 60 to less than 70 mg per deciliter (3.9 mmol per liter) were significantly reduced in the threshold-suspend group (P<0.001 for each range). After 1438 instances at night in which the pump was stopped for 2 hours, the mean sensor glucose value was 92.6±40.7 mg per deciliter (5.1±2.3 mmol per liter). Four patients (all in the control group) had a severe hypoglycemic event; no patients had diabetic ketoacidosis.

CONCLUSIONS

This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values.

Source: NEJM