Radiomics of Tumor Heterogeneity in 18F-FDG-PET-CT for Predicting Response to Immune Checkpoint Inhibition in Therapy-Naïve Patients with Advanced Non-Small-Cell Lung Cancer.

We aimed to evaluate the predictive and prognostic value of baseline 18F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy-chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into "responder" (n = 33) and "non-responder" (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for "PET-Skewness" and 0.75 predicting overall progression for "PET-Median". In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06-0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11-0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.

Hybrid CMR- and FDG-PET-Imaging Gives New Insights Into the Relationship of Myocardial Metabolic Activity and Fibrosis in Patients With Becker Muscular Dystrophy.

BACKGROUND: Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course. PURPOSE: Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach. METHODS: Hybrid CMR- and FDG-PET-imaging was performed in N = 14 patients with BMD on a whole-body Biograph mMR system (Siemens, Erlangen, Germany). The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 min starting with tracer injection. Uptake values from 60 to 65 min p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake. RESULTS: A characteristic pattern of LGE in the LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. There was one patient without any LGE. Segmental FDG uptake was 88 ± 6% in the LV lateral wall vs. 77 ± 10% in the septal wall (p < 0.001). There was an inverse relationship between segmental FDG activity compared to segmental LGE extent (r = -0.33, p = 0.089). There were N = 6 LGE-positive patients with a segmental difference in FDG uptake of >15% in the LV lateral wall compared to the septal wall = ΔFDG-high group (lateral FDG = 91±3% vs. septal FDG = 69±8%; p < 0.001) while the remaining N = 7 LGE-positive patients showed a segmental difference in FDG uptake of ≤ 15% = ΔFDG-low group (lateral FDG = 85±7% vs. septal FDG = 83 ± 5%; p = 0.37). Patients in the ΔFDG-high group showed only a minor difference in the LGE extent between the LV lateral wall vs. septal wall (p = 0.09) whereas large differences were observed in the ΔFDG-low group (p < 0.004). CONCLUSIONS: Segmental FDG uptake-reflecting myocardial metabolic activity-is higher in the LV free wall of BMD patients-possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.

Prevalence of hyperfunctioning thyroid nodules among those in need of fine needle aspiration cytology according to ATA 2015, EU-TIRADS, and ACR-TIRADS.

PURPOSE: Given the large number of patients with thyroid nodules, improvement of the specificity of current ultrasound-based thyroid nodule classification systems (ATA, EU-TIRADS, and ACR-TIRADS) is warranted to reduce the number of diagnostic thyroidectomies. Thyroid scintigraphy has been shown to demonstrate hyperfunctional nodules, associated with a low malignancy risk, in euthyroid patients. However, it is not known if thyroid scintigraphy could improve specificity of current classification systems. The aim of this study, therefore, was to determine the frequency of hyperfunctional nodules among those nodules in need of fine needle aspiration cytology (FNA) according to current classification systems and to test if nodule functional status is associated with sonographic features. METHODS: Five hundred sixty-six euthyroid patients (TSH 0.55-4.20 µU/ml) presenting for thyroid nodule workup including thyroid sonography and scintigraphy at our department between 09/2013 and 02/2018 were included in this retrospective study. All nodules > 10 mm were classified according to ATA, EU-TIRADS, and ACR-TIRADS and correlated to their functional status as assessed by 99mTc-pertechnetate scintigraphy. RESULTS: Ultrasound detected 1029 thyroid nodules ≥ 10 mm, including 545 nodules ≥ 15 mm. Prevalence of hyperfunctional nodules among those with recommendation for FNA according to ATA 2015, EU-TIRADS, and ACR-TIRADS was 6.4%, 6.9%, and 6.5% for nodules ≥ 10 mm and 7.2%, 7.6%, and 7.5% only considering nodules ≥ 15 mm. No sonographic feature was correlated to hyperfunctionality of nodules. CONCLUSION: In euthyroid patients, thyroid scintigraphy demonstrates hyperfunctionality, which cannot be predicted by ultrasound, in up to 6.9% of nodules in need of FNA according to ultrasound-based classifications. Given the known low risk of malignancy in hyperfunctional nodules, thyroid scintigraphy can lower the frequency of fine needle aspirations and-potentially-the frequency of diagnostic hemithyroidectomies in euthyroid patients.

Impact of presynaptic sympathetic imbalance in long-QT syndrome by positron emission tomography.

OBJECTIVE: We investigated the impact of cardiac presynaptic norepinephrine recycling in patients with long-QT syndrome (LQTS) using positron emission tomography (PET) with 11C-meta-hydroxyephedrine ([11C]mHED-PET). METHODS: [11C]mHED-PET was performed in 25 patients with LQTS (LQT1: n=14; LQT2: n=11) and 20 healthy controls and correlated with clinical parameters. [11C]mHED-PET images were analysed for global and regional retention indices (RI) and washout rates (WO) reflecting dynamic parameters of the tracer activity. RESULTS: Global and regional RI values were similar between patients with LQTS and controls. Although the global WO rates were similar between these groups, regional WO rates were on average higher in the lateral left ventricle (LV) wall in patients with LQTS (dose, mean ±SD; 0.08±0.14 vs 0.00%±0.09% min-1; p=0.033). In addition, patients with LQTS with a longer QTc interval showed a higher global WO rate. Clinical symptoms correlated with higher global WO rates. In the presence of normal global WO rates, asymptomatic LQTS patients showed higher global RI values. CONCLUSION: The increased regional WO rate of [11C]mHED in the lateral LV suggests an imbalance of presynaptic catecholamine reuptake and release, resulting in a higher synaptic catecholamine concentration, in particular in LQT1 patients. This might enhance ß-adrenoceptor signalling and thereby aggravate inherited ion channel dysfunction and may facilitate occurrence of ventricular tachyarrhythmias. Detection of regional differences in LV sympathetic nervous function may modify disease expression and potentially serve as a non-invasive risk marker in congenital LQTS. TRIAL REGISTRATION NUMBER: 2006-002767-41;Results.

Sex differences in absolute myocardial perfusion. Non-invasive H2(15)O-PET in young healthy adults.

AIM: To investigate sex differences in myocardial perfusion especially in healthy individuals since former studies are rare and findings are controversial. Participants, methods: 26 subjects were enrolled: 16 healthy women (age: 34 ±7 years) were compared with 10 healthy men (age: 34 ± 3 years; p = ns). Myocardial blood flow (MBF) and coronary vascular resistance (CVR) were quantified at rest, during adenosine infusion and cold-pressor-testing, using positron emission tomography and radioactive-labelled water (H2(15)O-PET). RESULTS: Women showed higher MBF than men at rest (1.10 ± 0.18 vs. 0.85 ± 0.20 ml/min/ml; p = 0.003) and cold-stress (1.39 ± 0.38 vs. 1.06 ± 0.28 ml/min/ml; p = 0.026). Corrected for rate-pressure-product, baseline findings maintained significance (1.41 ± 0.33 vs. 1.16 ± 0.19 ml/min/ml; p = 0.024). CVR was lower in women at baseline (81 ± 14 vs. 107 ± 22 mmHg*ml(-1)*min*ml; p = 0.006) and during cold-pressor-testing (71 ± 17 vs. 91 ± 20 mmHg*ml(-1)*min*ml; p = 0.013). Under adenosine neither maximal MBF (4.06 ± 1.0 vs. 3.91 ± 0.88 ml/min/ml; p = ns) nor coronary flow reserve (3.07 ± 1.12 vs. 3.44 ± 0.92; p = ns) nor CVR (24 ± 8 vs. 24 ± 6 mmHg*ml(-1)*min*ml; p = ns) showed sex-related differences. CONCLUSION: Women show higher myocardial perfusion and lower coronary vascular resistance than men in physiologic states. Maximum perfusion and vasodilation under adenosine are not sex-specific.

Microvascular dysfunction in nonfailing arrhythmogenic right ventricular cardiomyopathy.

PURPOSE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a nonischaemic cardiomyopathy and leading cause of sudden death in the young. It has been shown that microvascular dysfunction reflected by an impaired myocardial blood flow (MBF) response to stress is present in patients with other forms of nonischaemic cardiomyopathy, e.g. dilated cardiomyopathy, and that the reduced MBF may be related to a poor prognosis. Therefore, we quantified MBF, coronary flow reserve and coronary vascular resistance in patients with nonfailing ARVC using H(2)(15)O and PET. METHODS: In ten male patients with ARVC (mean age 49 ± 14 years), MBF was quantified at rest and during adenosine-induced hyperaemia using H(2)(15)O PET. Results were compared with those obtained in 20 age-matched healthy male control subjects (mean age 46 ± 14 years). RESULTS: Resting MBF was not significantly different between patients with ARVC and controls (MBF(rest) 1.19 ± 0.29 vs. 1.12 ± 0.20 ml/min/ml). However, hyperaemic MBF was significantly lower in patients with ARVC than in controls (2.60 ± 0.96 vs. 3.68 ± 0.84 ml/min/ml; p = 0.005). Consequently, patients with ARVC had a significantly lower coronary flow reserve than control subjects (2.41 ± 1.34 vs. 3.39 ± 0.93; p = 0.030). In addition, hyperaemic coronary vascular resistance was increased in patients with ARVC (36.79 ± 12.91 vs. 26.31 ± 6.49 mmHg × ml(-1) × min × ml; p = 0.007), but was found to be unchanged at rest. CONCLUSION: In this small well-characterized cohort of patients with nonfailing ARVC, we found a significantly reduced hyperaemic MBF and increased coronary vascular resistance. Further studies are necessary to corroborate this potential new functional aspect of the pathophysiological mechanisms underlying ARVC.

Cardiac sympathetic dysfunction in genotyped patients with arrhythmogenic right ventricular cardiomyopathy and risk of recurrent ventricular tachyarrhythmias.

UNLABELLED: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) typically present with ventricular tachyarrhythmias preferentially triggered by an elevated sympathetic tone. Previous studies demonstrated an impairment of the presynaptic catecholamine reuptake as assessed by (123)I-labeled norepinephrine analog on metaiodobenzylguanidine ((123)I-MIBG) SPECT. Mutations in the gene encoding for plakophilin-2 (PKP-2) are the most common cause of autosomal dominant ARVC (ARVC-9). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in patients with ARVC and correlated these findings with the causative genotype. METHODS: (123)I-MIBG SPECT was performed for 42 patients with definite ARVC (10 women, 32 men; mean age ± SD, 43 ± 14 y). Images were acquired at 4 h after injection and analyzed for regional (123)I-MIBG uptake in a standardized 33-segment polar map. Results were compared with those obtained from 10 control subjects (5 women, 5 men; mean age ± SD, 43 ± 12 y). RESULTS: An abnormal tracer uptake was detected in 25 patients with ARVC (59%). The extents of right ventricular dilation and regional wall motion abnormalities as well as electrocardiographic markers of de- or repolarization were not significantly different between patients with normal and abnormal (123)I-MIBG SPECT findings. However, during long-term follow-up of 11.9 ± 4.1 y, patients with abnormal (123)I-MIBG SPECT findings experienced life-threatening ventricular tachyarrhythmias significantly more often (22/25 patients [88%]) and independent of the extent of right ventricular dysfunction than those with a normal sympathetic innervation (6/17 patients [35%]; P < 0.0005). Mutations in PKP-2 were identified in 17 patients (40%) but were not correlated with the degree of adrenergic dysfunction. CONCLUSION: In patients with ARVC, an impairment of adrenergic innervation independent of the underlying genotype is associated with a higher incidence for future recurrences of ventricular tachyarrhythmias. This finding may suggest a potential role of (123)I-MIBG SPECT for individualized risk stratification in ARVC patients and asymptomatic PKP-2 mutation carriers alike.

Impaired cardiac sympathetic innervation in symptomatic patients with long QT syndrome.

PURPOSE: Increased sympathetic activation is a key modifier for arrhythmogenesis in patients with long QT syndrome (LQTS), a congenital channelopathy. Therefore, we investigated cardiac sympathetic function using 123I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) in a cohort of symptomatic LQTS patients and correlated these findings with the underlying genotype. METHODS: [123I]MIBG SPECT was performed in 28 LQTS patients. Among these, 18 patients (64%) had a previous syncope and 10 patients (36%) survived sudden cardiac arrest. Patients were characterized in terms of genetic subtypes and QTc interval on surface ECGs. SPECT images were analysed for regional [123I]MIBG uptake in a 33-segment bullseye scheme and compared to those obtained from 10 age-matched healthy control subjects (43±12 years). RESULTS: An abnormal 123I-MIBG scan was found in 17 of 28 LQTS patients (61%) with a tracer reduction mainly located in the anteroseptal segments of the left ventricle. This finding was independent of the genetic LQTS subtype. In addition, no differences were found between LQTS patients with a QTc>500 ms vs <500 ms or those suffering from syncope vs VF (p>0.05). CONCLUSION: A distinct regional pattern of impaired cardiac sympathetic function was identified in the majority of symptomatic LQTS patients. This innervation defect was independent of the underlying genotype and clinical disease expression.

Evaluation and comparison of 11C-choline uptake and calcification in aortic and common carotid arterial walls with combined PET/CT.

PURPOSE: Inflamed atherosclerotic plaques may rupture and cause acute myocardial infarction, stroke and other thrombotic events. Early detection of these unstable plaques could, in many cases, prevent such potentially fatal events. 11C-choline or 18F-labelled choline derivatives for visualizing the synthesis of phospholipids, are promising markers of plaque inflammation with potential advantages over 18F-FDG. Their potential for plaque characterization in humans is, however, unclear. In this study the prevalence and distribution of 11C-choline uptake in the aortic and common carotid arterial walls of elderly male patients was evaluated with combined PET/CT. Additionally, the localization of radiotracer uptake and calcification was correlated in various vessel segments. METHODS: Image data from 93 consecutive male patients between 60 and 80 years old who had undergone whole-body 11C-choline PET/CT assessment for prostate cancer were evaluated retrospectively. 11C-choline uptake and calcification were analysed qualitatively and semiquantitatively and compared. RESULTS: 11C-choline uptake was found in 95% of patients, calcification in 94% throughout all vessel segments. In 6% of the patients radiotracer uptake was colocalized with calcifications, whereas less than 1% of calcification sites showed increased radiotracer uptake. CONCLUSION: Both 11C-choline uptake and calcification in the aortic and common carotid arterial walls are common in elderly men. Radiotracer uptake and calcification are, however, only rarely colocalized. 11C-choline has the potential to provide information about atherosclerotic plaques independent of calcification measurement.

Myocardial perfusion in nonischemic dilated cardiomyopathy with and without atrial fibrillation.

UNLABELLED: Recent studies have shown that idiopathic atrial fibrillation (AF) is associated with diminished myocardial perfusion and perfusion reserve, which are also impaired in various forms of cardiomyopathies. In many cases, AF develops during progression of dilated cardiomyopathy (DCM) and may aggravate heart failure. This study compared myocardial perfusion between patients with nonischemic DCM with and without AF. METHODS: Twelve men (age +/- SD, 55 +/- 12 y) who had DCM and persistent AF were compared with a group of 18 men (mean age, 43 +/- 15 y, P = not statistically significant) who had DCM and sinus rhythm and with 22 healthy controls (mean age, 47 +/- 13 y, P = not statistically significant). Myocardial blood flow (MBF) was noninvasively quantified at rest and during adenosine infusion using PET and radioactive-labeled water (H(2)(15)O PET). RESULTS: Compared with controls, DCM patients without AF showed impaired hyperemic perfusion (2.52 +/- 1.29 vs. 3.57 +/- 0.88 mL/min/mL, P = 0.014) and perfusion reserve (2.10 +/- 1.01 vs. 3.37 +/- 0.97, P = 0.003). However, compared with DCM patients without AF, DCM patients with AF showed an additional impairment in resting perfusion (0.82 +/- 0.31 mL/min/mL, P = 0.010) and hyperemic perfusion (1.32 +/- 0.93 mL/min/mL, P = 0.022), and compared with controls, DCM patients with AF showed a further diminishment of perfusion reserve (1.68 +/- 0.94 vs. 3.37 +/- 0.97, P < 0.001) accompanied by the highest coronary vascular resistance of all groups. CONCLUSION: Compared with patients with sinus rhythm, patients with AF have significantly reduced myocardial perfusion reserve and increased coronary resistance in nonischemic DCM. Further studies on the underlying pathomechanisms are warranted.

Impaired myocardial perfusion and perfusion reserve associated with increased coronary resistance in persistent idiopathic atrial fibrillation.

AIMS: Patients with atrial fibrillation (AF) present with symptoms of myocardial ischaemia despite exclusion of coronary artery disease. A small vessel disease has been suggested. We quantified myocardial perfusion, perfusion reserve, and coronary vascular resistance (CVR) in AF patients using positron emission tomography (PET). METHODS AND RESULTS: Twenty-five male patients (age: 58 +/- 13 years) with persistent idiopathic AF were compared with 13 age- and risk-matched male controls (age: 56 +/- 8 years). Using H(2)(15)O-PET, myocardial blood flow (MBF) was quantified at rest, at hyperaemia (adenosine), and during cold-pressor-testing (CPT). Scans were repeated 4.1 +/- 2.3 months after cardioversion in 10 AF patients. In AF, resting MBF (0.95 +/- 0.19 vs. 1.14 +/- 0.22 mL/min/mL; P = 0.009), hyperaemic MBF (2.07 +/- 0.80 vs. 3.33 +/- 0.78 mL/min/mL; P < 0.001), and MBF under CPT (0.90 +/- 0.25 vs. 1.14 +/- 0.25 mL/min/mL; P < 0.014) were significantly reduced compared with matched controls. Hyperaemic CVR was increased in AF (47 +/- 21 vs. 29 +/- 7 mmHg x mL/min/mL; P = 0.012) but unchanged at rest and under CPT. After cardioversion, resting MBF and MBF under CPT in AF were similar to matched controls, however, hyperaemic MBF and CVR were not recovered. CONCLUSION: In AF, MBF at baseline, at hyperaemia, and at CPT is reduced, whereas CVR under hyperaemic conditions is increased. Following electrical cardioversion, these findings are partly reversible and therefore most likely secondary to the arrhythmia.

Molecular cardiovascular imaging using scintigraphic methods.

Molecular cardiovascular imaging plays an increasingly important role both in basic research and in clinical diagnosis. Scintigraphic methods have long been used to study pathophysiological changes on a cellular and molecular level, and they are likely to remain important molecular imaging modalities in the foreseeable future. This article provides an overview over current developments in cardiovascular molecular imaging using scintigraphic methods. The focus lies on imaging of cardiac innervation, plaque instability, hypoxia and angiogenesis, gene expression and stem and progenitor cell migration and proliferation.

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: validation of an elastic surface model approach in comparison to cardiac magnetic resonance imaging, 4D-MSPECT and QGS.

PURPOSE: The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method. METHODS: SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable. CONCLUSION: The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation.

PURPOSE: Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by (123)I-meta-iodo-benzylguanidine scintigraphy ((123)I-MIBG SPECT), on the long-term prognosis of patients with IVF. METHODS: (123)I-MIBG SPECT was performed in 20 patients (mean age 37+/-13 years) with IVF. Mean follow-up of patients after study entry was 7.2+/-1.5 years (range 4.9-10.5 years). Ten patients (five men, five women; mean age 43+/-12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group. RESULTS: Abnormal (123)I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal (123)I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal (123)I-MIBG uptake. CONCLUSION: Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of (123)I-MIBG SPECT during the long-term follow-up of these patients.

Abnormal myocardial presynaptic norepinephrine recycling in patients with Brugada syndrome.

BACKGROUND: Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. METHODS AND RESULTS: Nine patients with Brugada syndrome (6 male, 3 female; age, 41+/-13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11C-Hydroxyephedrine (11C-HED) and the nonselective beta-blocker 11C-CGP 12177 (11C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9+/-16.2 mL/g versus 69.1+/-14.2 mL/g; P<0.05), whereas postsynaptic beta-adrenoceptor density, assessed by 11C-CGP, was similar in patients and control subjects (10.4+/-6.7 pmol/g versus 10.2+/-2.9 pmol/g; P=NS). CONCLUSIONS: The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved beta-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.

Functional changes after partial left ventriculectomy and mitral valve repair assessed by gated perfusion SPECT.

UNLABELLED: A myocardial remodeling in dilated cardiomyopathy (DCM) after partial left ventriculectomy (PLV) has been previously discussed. The aim of this study was to investigate the functional changes in the follow-up of patients with DCM undergoing PLV using electrocardiographically triggered perfusion SPECT (gated SPECT). METHODS: Twelve DCM patients (10 men, 2 women; 56 +/- 9 y [mean +/- SD]), after successful PLV and mitral valve repair (PLV-MVR), were monitored by gated SPECT and echocardiography. Gated SPECT quantified end-diastolic volumes (EDV), end-systolic volumes (ESV), myocardial and scar volumes, as well as ejection fraction (EF) preoperatively, early (38 +/- 28 d), and late (296 +/- 130 d) after PLV-MVR. RESULTS: EDV and ESV showed an immediate reduction after PLV-MVR (EDV from 542 +/- 90 mL to 350 +/- 81 mL, P < 0.001; ESV from 452 +/- 91 mL to 254 +/- 79 mL, P < 0.001) with no significant change in the late follow-up (EDV late, 316 +/- 63 mL; ESV late, 207 +/- 63 mL; both P = not significant vs. early follow-up). PLV-MVR immediately improved EF (preoperative, 16.8% +/- 5.5%; early, 28.8% +/- 7.6%; P = 0.003) with no significant change in the late follow-up (36.0% +/- 9.4%; P = not significant vs. early follow-up). CONCLUSION: In this highly selected DCM patient group, gated perfusion SPECT assessed early responses in volumes and EF after PLV-MVR. However, although statistically nonsignificant in the small patient group, ESV and EDV were further decreased, whereas EF improved toward 1 y, coinciding with the improvement of clinical symptoms (New York Heart Association), potentially indicating a functional remodeling after PLV-MVR. Further studies in larger patient cohorts and longer follow-up are warranted.