Autonomic disorders and myocardial 123I-metaiodobenzylguanidine scintigraphy in Huntington's disease.

BACKGROUND: Huntington's disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl). METHODS: Fifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson's disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated. RESULTS: We did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR. CONCLUSIONS: Our study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.

A machine learning-based approach to directly compare the diagnostic accuracy of myocardial perfusion imaging by conventional and cadmium-zinc telluride SPECT.

BACKGROUND: We evaluated the performance of conventional (C) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride (CZT)-SPECT in a large cohort of patients with suspected or known coronary artery disease (CAD) and compared the diagnostic accuracy of the two systems using machine learning (ML) algorithms. METHODS AND RESULTS: A total of 517 consecutive patients underwent stress myocardial perfusion imaging (MPI) by both C-SPECT and CZT-SPECT. In the overall population, an excellent correlation between stress MPI data and left ventricular (LV) functional parameters measured by C-SPECT and by CZT-SPECT was observed (all P < .001). ML analysis performed through the implementation of random forest (RF) and k-nearest neighbors (NN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for k-NN) was greater than that of C-SPECT (88% for RF and 53% for k-NN). CONCLUSIONS: MPI data and LV functional parameters obtained by CZT-SPECT are highly reproducible and provide good correlation with those obtained by C-SPECT. ML approach showed that the accuracy and sensitivity of CZT-SPECT is greater than C-SPECT in detecting CAD.

Relationship between heart rate response and cardiac innervation in patients with suspected or known coronary artery disease.

BACKGROUND: Chronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD). METHODS AND RESULTS: We studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123I metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula: (peak HR - rest HR)/rest HR × 100. 123I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio < 1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02). CONCLUSIONS: The relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function.

Quantification of myocardial perfusion reserve by CZT-SPECT: A head to head comparison with 82Rubidium PET imaging.

BACKGROUND: We measured myocardial blood flow (MBF) and perfusion reserve (MPR) by dynamic CZT-SPECT and 82Rb-PET in patients with suspected or known coronary artery disease (CAD) and compared the accuracy of the two methods in predicting obstructive CAD. METHODS: Twenty-five patients with available coronary angiography data underwent 99mTc-sestamibi CZT-SPECT and 82Rb-PET cardiac imaging. Stress and rest MBF and MPR were calculated by both methods and compared. Diagnostic accuracies of CZT-SPECT and PET were also assessed using a receiver-operator-characteristic curve. RESULTS: CZT-SPECT yielded similar baseline MBF, but higher hyperemic MBF and MPR values compared to PET. There was a modest correlation between the two methods for MPR (r = 0.56, P < .01). MPR by CZT-SPECT showed a good ability in identify a reduced MPR by PET, with an area under the curve of 0.85. A MPR cut-off of 2.5 was identified by CZT-SPECT for detection of abnormal MPR by PET, with a sensitivity, specificity and accuracy of 86%, 73% and 80%. The area under the curve for the identification of obstructive CAD by regional MPR were 0.83 for CZT-SPECT and 0.84 for PET (P = .90). At CZT-SPECT, a regional MPR of 2.1 provided the best trade-off between sensitivity and specificity for identifying obstructive CAD. Diagnostic accuracy of CZT-SPECT and PET using respective cut-off values was comparable (P = .62). CONCLUSION: Hyperemic MBF and MPR values obtained by CZT-SPECT are higher than those measured by 82Rb-PET imaging, with a moderate correlation between the two methods. CZT-SPECT shows good diagnostic accuracy for the identification of obstructive CAD. These findings may encourage the use of this new technique to a better risk stratification and patient management.

Impact of body mass index on cardiac adrenergic derangement in heart failure patients: a 123I-mIBG imaging study.

PURPOSE: To assess the impact of body mass index (BMI) on cardiac adrenergic derangement, measured by iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging in heart failure (HF) patients. Overweight and obesity represent relevant health issues, and augmented sympathetic tone has been described in patients with increased BMI. An extensive literature supports that HF-dependent cardiac denervation, measured through mIBG parameters, is an independent predictor of cardiovascular outcomes and mortality. However, the influence of BMI on cardiac mIBG uptake has not been largely investigated. METHODS: We prospectively enrolled patients with systolic HF, collecting demographic, clinical, echocardiographic data, and mIBG imaging parameters. In order to detect the factors associated with mIBG parameters, a model building strategy, based on the Multivariable Fractional Polynomial algorithm, has been employed. RESULTS: We studied 249 patients with systolic HF, mean age of 66.4 ± 10.6 years, and mean left ventricular ejection fraction (LVEF) of 30.7% ± 6.4, undergoing cardiac 123I-mIBG imaging to assess HF severity and prognosis. Seventy-eight patients (31.3%) presented a BMI ≥ 30 kg/m2 and obese patients showed a significant reduction in early heart to mediastinum (H/M) ratio (1.66 ± 0.19 vs. 1.75 ± 0.26; p = 0.008) and a trend to reduction in washout rate (33.6 ± 18.3 vs. 38.1 ± 20.1; p = 0.092) compared with patients with BMI < 30 kg/m2. Multiple regression analysis revealed that BMI, age, and LVEF were significantly correlated with early and late H/M ratios. CONCLUSIONS: Results of the present study indicate that BMI, together with LVEF and age, is independently correlated with cardiac mIBG uptake in HF patients.

Added prognostic value of left ventricular shape by gated SPECT imaging in patients with suspected coronary artery disease and normal myocardial perfusion.

BACKGROUND: Left ventricular (LV) remodeling is associated with adverse cardiovascular events. We evaluated the added prognostic value of LV shape index (SI) assessed by gated single-photon emission tomography (SPECT) in patients without known coronary artery disease (CAD). METHODS AND RESULTS: We studied 674 patients with normal myocardial perfusion and normal LV ejection fraction (EF) on stress gated SPECT imaging. An automated software program was used to calculate end-diastolic and end-systolic LVSI. An LVSI ≤ 0.54 at end-systole was considered normal. Follow-up was 96% complete with a median follow-up of 37 months. During follow-up, 25 events occurred (3.8% cumulative event rate). Event-free survival was lower in patients with abnormal end-systolic LVSI (P < .001). Age (P = .021), diabetes (P = .048), and end-systolic LVSI (P < .001) were independent predictors of events. LVSI added prognostic information increasing the global chi-square of the model including age and diabetes from 15.15 to 25.97 (P < .001). The effect of diabetes on hazard ratio increased with increasing values of end-systolic LVSI. The probability of events at 48 months predicted by Weibull analysis progressively increased with increasing values of end-systolic LVSI and was higher in patients with diabetes as compared to those without. Decision curve analyses indicate that the model including end-systolic LVSI resulted in an increased net benefit between 5% and 30% threshold probability, indicating superior estimation of outcomes at low threshold probability levels. CONCLUSIONS: The evaluation of LVSI may identify patients with early-stage LV remodeling and at higher risk of adverse cardiac events, even in the presence of normal myocardial perfusion.

Comparing the Prognostic Value of Stress Myocardial Perfusion Imaging by Conventional and Cadmium-Zinc Telluride Single-Photon Emission Computed Tomography through a Machine Learning Approach.

We compared the prognostic value of myocardial perfusion imaging (MPI) by conventional- (C-) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride- (CZT-) SPECT in a cohort of patients with suspected or known coronary artery disease (CAD) using machine learning (ML) algorithms. A total of 453 consecutive patients underwent stress MPI by both C-SPECT and CZT-SPECT. The outcome was a composite end point of all-cause death, cardiac death, nonfatal myocardial infarction, or coronary revascularization procedures whichever occurred first. ML analysis performed through the implementation of random forest (RF) and k-nearest neighbors (KNN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for KNN) was greater than that of C-SPECT (88% for RF and 53% for KNN). A preliminary univariate analysis was performed through Mann-Whitney tests separately on the features of each camera in order to understand which ones could distinguish patients who will experience an adverse event from those who will not. Then, a machine learning analysis was performed by using Matlab (v. 2019b). Tree, KNN, support vector machine (SVM), Naïve Bayes, and RF were implemented twice: first, the analysis was performed on the as-is dataset; then, since the dataset was imbalanced (patients experiencing an adverse event were lower than the others), the analysis was performed again after balancing the classes through the Synthetic Minority Oversampling Technique. According to KNN and SVM with and without balancing the classes, the accuracy (p value = 0.02 and p value = 0.01) and recall (p value = 0.001 and p value = 0.03) of the CZT-SPECT were greater than those obtained by C-SPECT in a statistically significant way. ML approach showed that although the prognostic value of stress MPI by C-SPECT and CZT-SPECT is comparable, CZT-SPECT seems to have higher accuracy and recall.

Outcome of Patients With Differentiated Thyroid Cancer Treated With 131-Iodine on the Basis of a Detectable Serum Thyroglobulin Level After Initial Treatment.

Background: In patients with differentiated thyroid cancer (DTC) and raising serum thyroglobulin (Tg) after total or near-total thyroidectomy and 131I remnant ablation an empiric 131I therapy may be considered. However, outcome data after empiric therapy in did not show a clear evidence of improved survival. We assessed the efficacy of such empiric 131I therapy in patients with DTC and evaluated the long-term outcome. Methods: A total of 100 patients with DTC showing raised Tg level during follow-up after thyroidectomy and 131I ablation were treated with a further 131I therapy (6.1 ± 1.7 GBq). Whole-body scan (WBS) was performed 5-7 days after therapy. Tg value at 12 months after 131I therapy was considered as an indicator of treatment response: ≤1.5 ng/ml complete remission (CR), >50% decrease partial remission (PR), higher than pre-therapy progression disease (PD), all other cases stable disease (SD). Patients were followed-up for 96 ± 75 months. Results: After 12 months, 62% of patients were in CR, 16% in PR, 8% in SD, and 14% in PD. WBS was positive in 41% of patients and negative in 59% (P = NS). Among patients with local recurrences at WBS 89% showed either CR or PR, while 71% of patients with distant metastases were in SD or PD (P < 0.001). Distant metastases at WBS (P < 0.05), CR (P < 0.0001), and CR + PR (P < 0.0001) were predictors of both progression free survival and overall survival. Conclusion: There is a beneficial effect of 131I therapy on outcome of patients with DTC treated on the basis of elevated Tg value. In these patients, survival is affected by achievement of CR or PR at 12 months evaluation after 131I therapy and by the presence of distant metastases at WBS.