Prognostic usefulness of planar 123I-MIBG scintigraphic images of myocardial sympathetic innervation in congestive heart failure: Follow-Up data from ADMIRE-HF.

BACKGROUND: To evaluate whether planar 123I-MIBG myocardial scintigraphy predicts risk of death in heart failure (HF) patients up to 5 years after imaging. METHODS AND RESULTS: Subjects from ADMIRE-HF were followed for approximately 5 years after imaging (964 subjects, median follow-up 62.7 months). Subjects were stratified according to the heart/mediastinum (H/M) ratio (< 1.60 vs ≥ 1.60) on planar 123I-MIBG scintigraphic images obtained at baseline in ADMIRE-HF. Cox proportional hazards models and Kaplan-Meier analyses were used to evaluate time to death, cardiac death, or arrhythmic events for subjects stratified by H/M ratio, baseline left ventricular ejection fraction (LVEF: < 25% and 25 to ≤ 35%), and by H/M strata within LVEF strata. All-cause mortality was 38.4% vs 20.9% and cardiac mortality was 16.8% vs 4.5%, in subjects with H/M < 1.60 vs ≥ 1.60, respectively (P < 0.05 for both comparisons). Subjects with preserved sympathetic innervation of the myocardium (H/M ≥ 1.60) were at significantly lower risk of all-cause and cardiac death, arrhythmic events, sudden cardiac death, or potentially life-threatening arrhythmias. Within LVEF strata, a trend toward a higher mortality for subjects with H/M < 1.60 was observed reaching significance for LVEF 25 to ≤ 35% only. CONCLUSIONS: During a median follow-up of 62.7 months, patients with H/M ≥ 1.60 were at significantly lower risk of death and arrhythmic events independently of LVEF values.

Clinical significance of incidental findings on coronary CT angiography: Insights from a randomized controlled trial.

BACKGROUND: The effect of incidental findings from coronary computed tomography angiography (CCTA) on management has not been rigorously investigated. This study uses a control group to explore this relationship. METHODS: Analysis of data from a randomized controlled trial of acute chest pain patients admitted to telemetry was performed. Patients were randomized to undergo either CCTA (n = 200) or radionuclide myocardial perfusion imaging (MPI) (n = 200). Incidental findings were determined from imaging reports. Records were reviewed to determine subsequent management and imaging during and after hospitalization. Comparisons were performed using Fischer's exact tests. RESULTS: 386 incidental findings were found among 187 CCTA studies. No extra-cardiac incidental findings were noted in the MPI arm, which served as an effective control group. There were significantly more non-coronary medical workups during admission in the CCTA group compared to the MPI group [20% (39) vs. 12% (23), P = 0.038]. CCTA patients underwent significantly more resting echocardiography during the inpatient workup compared to the MPI group [38% (75) vs. 18% (55), P = 0.042]. CCTA patients underwent significantly more non-contrast chest CT exams in the year following admission compared to MPI patients [14% (27) vs. 7% (13) P = 0.029]. CONCLUSIONS: Incidental findings on inpatient CCTAs performed for chest pain have a significant impact on treatment and imaging during and following hospital admission.

How do we establish cardiac sympathetic nervous system imaging with 123I-mIBG in clinical practice? Perspectives and lessons from Japan and the US.

Cardiac denervation is associated with progressive left ventricular (LV) dysfunction, ventricular arrhythmias, and sudden cardiac death (SCD) in heart failure (HF). In this regard, it is important to evaluate cardiac-specific sympathetic nervous system (SNS) function. The radiotracer Iodine-123 meta-iodobenzylguanidine (123I-mIBG) can noninvasively evaluate pre-synaptic SNS function. Recent multicenter trials have shown 123I-mIBG to have strong predictive value for fatal arrhythmias and cardiac death in HF. 123I-mIBG was initially developed in the USA in the 1970s. In 1992, the Japanese Ministry of Health and Labour approved 123I-mIBG for the assessment of cardiac function. Following approval, the Japanese nuclear cardiology community developed 123I-mIBG imaging services in various medical centers. Japanese groups have been trying to establish the clinical utility of 123I-mIBG and standardize parameters for data acquisition and image analysis. The US Food and Drug Administration (FDA) has approved clinical use of 123I-mIBG for cardiac and non-cardiac imaging. However, clinical use of 123I-mIBG in the US has been very limited. The number of 123I-mIBG studies in Japan has also been limited. There are similarities and differences between the two countries. To establish the clinical utility of 123I-mIBG in both countries, it is important to characterize the situations of 123I-mIBG in each.

Assessment of 123I-mIBG and 99mTc-tetrofosmin single-photon emission computed tomographic images for the prediction of arrhythmic events in patients with ischemic heart failure: Intermediate severity innervation defects are associated with higher arrhythmic risk.

RATIONALE: 123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs). METHODS: 123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2 years. RESULTS: 471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, P = 0.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities. CONCLUSIONS: The presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.

Current Clinical Applications and Next Steps for Cardiac Innervation Imaging.

PURPOSE OF REVIEW: Autonomic innervation is crucial for regulating cardiac function. Sympathetic innervation imaging with 123I-mIBG and analogous PET tracers assesses disease in ways that differ from customary methods. This review describes practical use in various clinical scenarios, discusses recent guidelines, presents new data confirming risk stratification power, describes an ongoing prospective study, and looks forward to wider use in patient management. RECENT FINDINGS: ASNC 123I-mIBG guidelines are available, expanding on European guidelines. ADMIRE-HF patient follow-up increased to 2 years in ADMIRE HFX, demonstrating independent mortality risk reclassification. ADMIRE-HF findings were substantiated in a Japanese consortium study and in the PAREPET 11C-HED PET study. Exciting potential uses of adrenergic imaging are management of LVADs and VT ablation. CZT cameras provide advantages, but derived parameters differ from Anger camera values. Independent risk stratification utility of adrenergic imaging with 123I-mIBG and PET tracers is continuously being confirmed. An ongoing prospective randomized study promises to establish patient management utility. There is potential for wider use and improved images with newer cameras and PET.

Coronary Computed Tomography Angiography Versus Radionuclide Myocardial Perfusion Imaging in Patients With Chest Pain Admitted to Telemetry: A Randomized Trial.

BACKGROUND: The role of coronary computed tomography angiography (CCTA) in the management of symptomatic patients suspected of having coronary artery disease is expanding. However, prospective intermediate-term outcomes are lacking. OBJECTIVE: To compare CCTA with conventional noninvasive testing. DESIGN: Randomized, controlled comparative effectiveness trial. (ClinicalTrials.gov: NCT00705458). SETTING: Telemetry-monitored wards of an inner-city medical center. PATIENTS: 400 patients with acute chest pain (mean age, 57 years); 63% women; 54% Hispanic and 37% African-American; and low socioeconomic status. INTERVENTION: CCTA or radionuclide stress myocardial perfusion imaging (MPI). MEASUREMENTS: The primary outcome was cardiac catheterization not leading to revascularization within 1 year. Secondary outcomes included length of stay, resource utilization, and patient experience. Safety outcomes included death, major cardiovascular events, and radiation exposure. RESULTS: Thirty (15%) patients who had CCTA and 32 (16%) who had MPI underwent cardiac catheterization within 1 year. Fifteen (7.5%) and 20 (10%) of these patients, respectively, did not undergo revascularization (difference, -2.5 percentage points [95% CI, -8.6 to 3.5 percentage points]; hazard ratio, 0.77 [CI, 0.40 to 1.49]; P = 0.44). Median length of stay was 28.9 hours for the CCTA group and 30.4 hours for the MPI group (P = 0.057). Median follow-up was 40.4 months. For the CCTA and MPI groups, the incidence of death (0.5% versus 3%; P = 0.12), nonfatal cardiovascular events (4.5% versus 4.5%), rehospitalization (43% versus 49%), emergency department visit (63% versus 58%), and outpatient cardiology visit (23% versus 21%) did not differ. Long-term, all-cause radiation exposure was lower for the CCTA group (24 versus 29 mSv; P < 0.001). More patients in the CCTA group graded their experience favorably (P = 0.001) and would undergo the examination again (P = 0.003). LIMITATION: This was a single-site study, and the primary outcome depended on clinical management decisions. CONCLUSION: The CCTA and MPI groups did not significantly differ in outcomes or resource utilization over 40 months. Compared with MPI, CCTA was associated with less radiation exposure and with a more positive patient experience. PRIMARY FUNDING SOURCE: American Heart Association.

Impact of medications on mIBG uptake, with specific attention to the heart: Comprehensive review of the literature.

BACKGROUND: A critical review of the literature on drug interactions with mIBG uptake was performed to allow formulation of contemporary guidance regarding withholding medications prior to clinical imaging studies. METHODS: Published information was extracted on the experimental system used, the quantitative characteristics of the measurements, and whether any data directly examining cardiac tissues were included. Level of evidence for each medication category was assessed on a qualitative scale of very low, low, medium, or high. Strength of medication effect for inhibition of mIBG uptake was judged as none, weak, moderate, or strong. RESULTS: The only medications for which level of evidence was judged high were labetalol and reserpine. Level of evidence was judged medium for tricyclic antidepressants, calcium channel blockers, and antiarrhythmics (specifically amiodarone). Evidence was judged sufficient to recommend withholding labetalol and the tricyclic antidepressants prior to mIBG cardiac imaging. Mechanistic evidence was sufficient to suggest consideration of withdrawal of sympathomimetic amines and serotonin-norepinephrine reuptake inhibitors (SNRIs). CONCLUSIONS: As there is strong evidence for inhibition of mIBG uptake in only a small number of compounds, clinical decisions regarding withdrawal of concomitant medications should be individualized by considering the potential consequences of a false-positive (artificially low cardiac uptake) imaging result.

A prediction model for 5-year cardiac mortality in patients with chronic heart failure using ¹²³I-metaiodobenzylguanidine imaging.

PURPOSE: Prediction of mortality risk is important in the management of chronic heart failure (CHF). The aim of this study was to create a prediction model for 5-year cardiac death including assessment of cardiac sympathetic innervation using data from a multicenter cohort study in Japan. METHODS: The original pooled database consisted of cohort studies from six sites in Japan. A total of 933 CHF patients who underwent (123)I-metaiodobenzylguanidine (MIBG) imaging and whose 5-year outcomes were known were selected from this database. The late MIBG heart-to-mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox proportional hazard and logistic regression analyses were used to select appropriate variables for predicting 5-year cardiac mortality. The formula for predicting 5-year mortality was created using a logistic regression model. RESULTS: During the 5-year follow-up, 205 patients (22 %) died of a cardiac event including heart failure death, sudden cardiac death and fatal acute myocardial infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis selected four parameters, including New York Heart Association (NYHA) functional class, age, gender and left ventricular ejection fraction, without HMR (model 1) and five parameters with the addition of HMR (model 2). The net reclassification improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR and its inclusion was most effective in the downward reclassification of low-risk patients. Nomograms for predicting 5-year cardiac mortality were created from the five-parameter regression model. CONCLUSION: Cardiac MIBG imaging had a significant additive value for predicting cardiac mortality. The prediction formula and nomograms can be used for risk stratifying in patients with CHF.

Rationale and design of a randomized trial comparing initial stress echocardiography versus coronary CT angiography in low-to-intermediate risk emergency department patients with chest pain.

BACKGROUND: Comparative effectiveness research (CER) has become a major focus of cardiovascular disease investigation to optimize diagnosis and treatment paradigms and decrease healthcare expenditures. Acute chest pain is a highly prevalent reason for evaluation in the Emergency Department (ED) that results in hospital admission for many patients and excess expense. Improvement in noninvasive diagnostic algorithms can potentially reduce unnecessary admissions. OBJECTIVE: To compare the performance of treadmill stress echocardiography (SE) and coronary computed tomography angiography (CTA) in ED chest pain patients with low-to-intermediate risk of significant coronary artery disease. DESIGN: This is a single-center, randomized controlled trial (RCT) comparing SE and CTA head-to-head as the initial noninvasive imaging modality. The primary outcome measured is the incidence of hospitalization. The study is powered to detect a reduction in admissions from 28% to 15% with a sample size of 400. Secondary outcomes include length of stay in the ED/hospital and estimated cost of care. Safety outcomes include subsequent visits to the ED and hospitalizations, as well as major adverse cardiovascular events at 30 days and 1 year. Patients who do not meet study criteria or do not consent for randomization are offered entry into an observational registry. CONCLUSIONS: This RCT will add to our understanding of the roles of different imaging modalities in triaging patients with suspected angina. It will increase the CER evidence base comparing SE and CTA and provide insight into potential benefits and limitations of appropriate use of treadmill SE in the ED.

High-Output Heart Failure in Multiple Myeloma: Novel Application of Tc-99m MAA to Identify Intramedullary Shunting.

We introduce the innovative use of technetium-99m-labeled macroaggregated albumin to diagnose high-output heart failure in a patient with multiple myeloma with persistent congestion symptoms. Symptom resolution occurred with lenalidomide and steroids. This marks the first clinical use of technetium-99m-labeled macroaggregated albumin for clarifying high-output heart failure etiology.

Cardiac autonomic imaging with SPECT tracers.

Radionuclide cardiac imaging has potential to assess underlying molecular, electrophysiologic, and pathophysiologic processes of cardiac disease. An area of current interest is cardiac autonomic innervation imaging with a radiotracer such as (123)I-meta-iodobenzylguanidine ((123)I-mIBG), a norepinephrine analogue. Cardiac (123)I-mIBG uptake can be assessed by planar and SPECT techniques, involving determination of global uptake by a heart-to-mediastinal ratio, tracer washout between early and delayed images, and focal defects on tomographic images. Cardiac (123)I-mIBG findings have consistently been shown to correlate strongly with heart failure severity, pre-disposition to cardiac arrhythmias, and poor prognosis independent of conventional clinical, laboratory, and image parameters. (123)I-mIBG imaging promises to help monitor a patient's clinical course and response to therapy, showing potential to help select patients for an ICD and other advanced therapies better than current methods. Autonomic imaging also appears to help diagnose ischemic heart disease and identify higher risk, as well as risk-stratify patients with diabetes. Although more investigations in larger populations are needed to strengthen prior findings and influence modifications of clinical guidelines, cardiac (123)I-mIBG imaging shows promise as an emerging technique for recognizing and following potentially life-threatening conditions, as well as improving our understanding of the pathophysiology of various diseases.