Observer experience and accuracy of 18F-sodium-fluoride PET/CT for the diagnosis of bone metastases in prostate cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients. METHODS: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0. RESULTS: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively. CONCLUSION: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands.

An Algorithm for Individual Dosage in Cadmium-Zinc-Telluride SPECT-Gated Radionuclide Angiography.

The aim of the present study was to test an individualised dose without compromising the ease of analysing data when performing equilibrium radionuclide angiography (ERNA) using cadmium-zinc-telluride (CZT) SPECT. From March 2018 to January 2019, 1650 patients referred for ERNA received either an individualised dose of 99mTc-labeled human serum albumin (HSA) according to their age, sex, height, and weight (n = 1567), or a standard dose of 550 MBq (n = 83). The target count rate (CRT) was reduced every two months from 2.7 to 1.0 kcps. A final test with a CRT of 1.7 kcps was run for three months to test whether an agreement within 2% points for the determination of LVEF, on the basis of only two analyses, was obtainable in at least 95% of acquisitions. All the included ERNAs were performed on a dedicated cardiac CZT SPECT camera. When using the algorithm for an individualised dose, we found that agreement between the measured and predicted count rate was 80%. With a CRT of 1.7 kcps, the need for more than two analyses to obtain sufficient agreement for LVEF was 4.9%. Furthermore, this resulted in a mean dose reduction from 550 to 258 MBq. Patients' weight, height, sex, and age can, therefore, be used for individualising a tracer dose while reducing the mean dose.

Locating hyperfunctioning parathyroid glands using 11C-Choline PET/CT: an inter- and intra-observer variation study.

BACKGROUND: Use of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases. PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss' kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard. RESULTS: Intra-observer agreement was 'good' to 'near perfect' for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were 'high' in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts. CONCLUSION: 11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline. The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

The Value of 68Ga-PSMA PET/CT Following Equivocal 18F-NaF PET/CT in Prostate Cancer Patients.

BACKGROUND: Inconclusive bone scans are a challenge but there is no consensus about follow-up imaging. We evaluated the use of 68gallium-labelled prostate-specific membrane antigen (68Ga-PSMA) PET/CT if 18F-sodium fluoride (18F-NaF) PET/CT was inconclusive. METHODS: This retrospective study included patients with no previously known bone metastases who had one or more equivocal bone lesions on 18F-NaF PET/CT and underwent additional 68Ga-PSMA PET/CT. The bone lesions were deemed as true metastases or not based on follow-up by surveying supplemental imaging modalities and hospital records. A subgroup of patients with "most valid follow-up" was created, which included patients with unmeasurable PSA after prostatectomy or subsequent imaging (additional 18F-NaF PET/CT, 68Ga-PSMA PET/CT, CT, or MRI). RESULTS: Of the 2918 patients referred for 18F-NaF PET/CT from the department of urology in the inclusion period, 51 (1.7%) were inconclusive regarding bone metastases and underwent additional 68Ga-PSMA PET/CT. Thirteen of these patients (25%) were ultimately diagnosed with bone metastases. Patient-based sensitivity, specificity, and accuracy of additional 68Ga-PSMA PET/CT were 100%, 95%, and 96%, respectively. In patients with "most valid follow-up", the same parameters were 100%, 93%, and 94%, respectively. CONCLUSION: 68Ga-PSMA PET/CT is an excellent complementary modality in when 18F-NaF PET/CT is equivocal.

Clinical usefulness of FDG-PET/CT for identification of abnormal extra-cardiac foci in patients with infective endocarditis.

The aim of the study was to evaluate the ability to detect extra-cardiac foci by means of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with definite endocarditis (IE) according to the modified Duke criteria and investigate the clinical impact of the findings. From January 2011 to December 2015 we included 178 patients (mean age 66 ± 14 years, 25% female) with IE in this multicentre study. FDG-PET/CT was part of the work-up for extra-cardiac foci in the including hospitals and was performed at a median of 9 days (IQR 10) after IE was diagnosed. In 114 patients FDG-PET/CT identified 166 lesions: 52 (31%) infectious lesions, 21 (13%) cases of cancer, 7 (4%) cases of embolism, 60 (36%) reactive findings, and 26 (16%) other types of lesions. A total of 74 new extra-cardiac findings, not previously discovered by other modalities, were identified in 62 patients and resulted in additional investigations in 29 patients and a change in treatment in 18 patients (10%). The most frequent diagnoses discovered by FDG-PET/CT were colon polyps, cancer, and spondylodiscitis. There was a higher rate of findings leading to a change in treatment in patients above 67 years of age infected with other bacterial aetiologies than streptococci. FDG-PET/CT was useful to detect extra-cardiac foci. FDG-PET/CT findings may lead to unnecessary investigations. One out of 10 the patients with definite endocarditis had underwent a change in treatment regimen based on the FDG-PET/CT findings.

Ventricular peak emptying and filling rates measured by gated tomographic radionuclide angiography using a cadmium-zinc-telluride SPECT camera in chemotherapy-naïve cancer patients.

INTRODUCTION: Radionuclide angiography is widely used for left ventricular function assessment. This study establishes normative data and inter-study repeatability on peak ventricular filling and emptying rates obtained by a cadmium-zinc-telluride SPECT camera. METHOD: Cancer patients (N = 764) without diabetes or cardiovascular diseases referred for baseline assessment of cardiac function were included. Repeatability was assessed in 46 patients where two separate acquisitions were performed. Left and right ventricular emptying rates (LPER, RPER) and filling rates (LPFR, RPFR) were obtained and whenever possible also atrial filling rates (PFRa). RESULTS: Filling rates were higher in women than men. Emptying rates tended to increase with age, whereas filling rates and the E/A ratio decreased. One patient was excluded from the repeatability analysis due to an unexplained high intra-observer variation. Intraclass correlation coefficients for LPER, RPER, LPFR, and RPFR were 0.99, 0.94, 0.99, and 0.84, no proportional biases were detected. CONCLUSION: Reference values and relations to age and gender in chemotherapy-naïve cancer patients without cardiopulmonary disease are presented. The CZT camera provides reproducible estimates of peak emptying and filling rates.

Observer Agreement and Accuracy of 18F-Sodium Fluoride PET/CT in the Diagnosis of Bone Metastases in Prostate Cancer.

Our aim was to evaluate the interobserver agreement in 18F-sodium fluoride (NaF) PET/CT for the detection of bone metastases in patients with prostate cancer (PCa). Methods:18F-NaF PET/CT scans were retrieved from all patients who participated in 4 recent prospective trials. Two experienced observers independently evaluated the 18F-NaF PET/CT scans on a patient level using a 3-category scale (no bone metastases [M0], equivocal for bone metastases, and bone metastases present [M1]) and on a dichotomous scale (M0/M1). In patients with no more than 10 lesions, the location and number of lesions were recorded. On a patient level, the diagnostic performance was calculated using a sensitivity analysis, in which equivocal lesions were handled as M0 as well as M1. Results:18F-NaF PET/CT scans from 219 patients with PCa were included, of whom 129 patients were scanned for primary staging, 67 for biochemical recurrence, and 23 for metastatic castration-resistant PCa. Agreement between the observers was almost perfect on a patient level (3-category unweighted κ = 0.83 ± 0.05, linear weighted κ = 0.90 ± 0.06, and dichotomous κ = 0.91 ± 0.07). On a lesion level (dichotomous scale), the observers agreed on the number and location of bone metastases in 205 (93.6%) patients. In the remaining 14 patients, the readers disagreed on the number of lesions in 13 patients and the location of bone metastases in 1 patient. A final diagnosis of bone metastases was made for 211 of 219 patients. The sensitivity ranged from 0.86 to 0.92, specificity from 0.83 to 0.97, positive predictive value from 0.70 to 0.93, and negative predictive value from 0.94 to 0.96. Conclusion: The interobserver agreement on 18F-NaF PET/CT for the detection of bone metastases in patients with PCa was very high among trained observers, both on a patient level and on a lesion level. Moreover, the diagnostic performance of 18F-NaF PET/CT was satisfactory, rendering 18F-NaF PET/CT a robust tool in the diagnostic armamentarium.

No Added Value of 18F-Sodium Fluoride PET/CT for the Detection of Bone Metastases in Patients with Newly Diagnosed Prostate Cancer with Normal Bone Scintigraphy.

The aim of this study was to determine if additional 18F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels < 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level ≥ 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy.

The influence of anthropometric and basic circulatory variables on count rate in cadmium-zinc-telluride SPECT gated radionuclide angiography.

AIM: To determine the influence of weight, height, gender, age, heart rate, and blood pressure on count rate in cadmium-zinc-telluride single-photon emission computed tomography (CZT SPECT) gated radionuclide angiography. METHOD: A total of 1,065 eligible patients referred for routine assessment of left ventricular ejection fraction were registered from August 2015 to November 2016. Data were recorded on heart rate, systolic and diastolic blood pressure, age, gender, height, weight, and count rate. All radionuclide angiographies were performed on a dedicated cardiac CZT SPECT camera, GE Discovery 530c. A dose of 550 MBq 99mTc-labeled human serum albumin was administered intravenously to each patient. RESULTS: Count rate varied from 1.2 to 8.9 counts per second. All test variables were significantly associated with count rate. From the preliminary analysis, weight appeared as the main contributing factor for explaining the variations in count rate with and R2 of 0.68. A model consisting of weight, height, gender, and age explains 75% of the variance in count rate. CONCLUSION: Patient height, weight, gender, and age have significant impact on count rate when performing CZT radionuclide angiography and may subsequently be used for individualized planning of tracer dosage.

Prospective comparison of 68Ga-PSMA PET/CT, 18F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer.

PURPOSE: To prospectively compare diagnostic accuracies for detection of bone metastases by 68Ga-PSMA PET/CT, 18F-NaF PET/CT and diffusion-weighted MRI (DW600-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR). METHODS: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68Ga-PSMA PET/CT, a 18F-NaF PET/CT and a DW600-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm2). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic. RESULTS: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for 68Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90-0.98 and 0.90-0.94 for 18NaF PET/CT (n = 67 patients); and 0.25-0.38, 0.87-0.92 and 0.59-0.62 for DW600-MRI (n = 60 patients). The diagnostic performance of DW600-MRI was significantly lower than that of 68Ga-PSMA PET/CT and 18NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68Ga-PSMA PET/CT and 18NaF PET/CT (p = 0.65). CONCLUSION: 68Ga-PSMA PET/CT and 18F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW600-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

Prospective comparative study of 18F-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer.

AIM: To compare 18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment. MATERIAL AND METHODS: Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1-3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses. RESULTS: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval 0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy. CONCLUSION: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.

Advanced Electrocardiogram Analysis in the Amitriptyline-poisoned Pig Treated with Activated Charcoal Haemoperfusion.

Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.

Diagnostic test accuracy study of 18F-sodium fluoride PET/CT, 99mTc-labelled diphosphonate SPECT/CT, and planar bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer.

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort.

[18F-FDG PET/CT contributes to diagnostics and therapy monitoring of radiation-induced angiosarcoma].

Angiosarcomas are rare, aggressive malignant mesenchymal tumours with a poor prognosis. Radiation therapy is an independent risk factor for the development of secondary angiosarcoma. The onset of angiosarcoma may resemble benign lesions, leading to delayed diagnosis. It has been suggested that 18F-fluorodeoxyglucose (FDG) PET/CT scan may be useful in the early diagnosis in differentiating angiosarcoma from benign lesions and in therapy monitoring. We report the utility of 18F-FDG PET/CT scan in the diagnosis and follow-up of radiation-induced angiosarcoma in a patient previously treated for uterine cancer.

Coronary artery calcium score and N-terminal pro-B-type natriuretic peptide as potential gatekeepers for myocardial perfusion imaging.

Myocardial perfusion imaging (MPI) holds an important place as non-invasive risk assessment in patients with intermediate risk of coronary heart disease (CHD). However, as much as 60-70% of MPI scans are normal. This study evaluates the role of coronary artery calcium scoring (CAC score) and NT-proBNP as potential gatekeepers for MPI. Patients with intermediate risk of CHD referred for standard MPI were included. CAC score and NT-proBNP were both assessed at the day of the stress study. Sensitivity, specificity and NPV for prediction of abnormal MPI scans were calculated for CAC, NT-proBNP and the combination hereof. A total of 190 patients were included (mean age 61 ± 12 years, 55% female) of whom 24% had known CHD. In all 30% of the scans were abnormal. CAC score achieved the highest AUC regardless of whether patients with known CHD were included or not [AUC 0·75 95% CI (0·66-0·84) and AUC 0·79 (0·68-0·91)]. As a singular variable, CAC score was the most potent predictor with a sensitivity of 85%, specificity of 39% and NPV 88%. The combination of CAC score<10 and NT-proBNP>26 reached a sensitivity of 98% and NPV 94%, where 8% of scans tentatively could be avoided. In patients referred for MPI with intermediate risk for CHD, a combination of CAC score and NT-proBNP could be used to identify a group of patients where MPI could be averted with a high degree of diagnostic safety.

Pre-chemotherapy values for left and right ventricular volumes and ejection fraction by gated tomographic radionuclide angiography using a cadmium-zinc-telluride detector gamma camera.

BACKGROUND: Estimation of left ventricular ejection fraction (LVEF) using equilibrium radionuclide angiography is an established method for assessment of left ventricular function. The purpose of this study was to establish normative data on left and right ventricular volumes and ejection fraction, using cadmium-zinc-telluride SPECT camera. METHODS AND RESULTS: From routine assessments of left ventricular function in 1172 patients, we included 463 subjects (194 men and 269 women) without diabetes, previous potentially cardiotoxic chemotherapy, known cardiovascular or pulmonary disease. The lower limits defined as mean value minus two standard deviations for ventricular ejection fraction and end diastolic volume were LVEF (men: 50%, women: 50%), LEDV (men: 45 mL, women: 40 mL), RVEF (men: 29%, women: 28%), and REDV (men: 73 mL, women: 57 mL).There was a significant negative correlation between age and both left and right ventricular volumes in women (r = -0.4, P < .001) but only for right end systolic ventricular volume in men (r = -0.3, P = .001). CONCLUSION: A set of reference values for cardiac evaluation prior to chemotherapy in cancer patients without other known cardiopulmonary disease is presented. There are age-related changes in cardiac dimensions with age depending on gender, although with only limited influence on LVEF or RVEF.

Tilt-table testing of patients with pacemaker and recurrent syncope.

The diagnosis of recurrent syncope in patients with pacemakers (PM) is quite challenging and the etiology of syncope is often multifactorial. To portray the mechanism of syncope in PM patients, we report the results of head-up tilt table testing (HUT) in a series of patients with PM, originally implanted for reasons other than neurally mediated syncope, referred due to syncope or pre-syncope (aborted syncope, vertigo, suspected orthostatic hypotension). Forty-one patients with PM undergoing a HUT in our syncope unit between January 1st, 2007 and December 31st 2011 were included. A standard HUT protocol with nitroglycerine provocation was used and the test results were classified according to current guidelines. Baseline data were retrieved from the medical records. Overall, 54% of patients had a positive response to HUT. Vasodepressor or orthostatic hypotensive response were the most prevalent responses accounting for 72% of patients with a positive test. There were no differences between groups with positive or negative test result regarding age, gender, resting blood pressure and heart rate, daily fluid intake, pacing mode, pacing indication or pacing rhythm at rest. HUT in patients with pacemakers has a high diagnostic yield. Although, the majority of patients had a vasodepressor or orthostatic hypotensive response, cardioinhibitory response leading to syncope was also seen.

Heritability of Tpeak-Tend interval and T-wave amplitude: a twin study.

BACKGROUND: Tpeak-Tend interval (TpTe) and T-wave amplitude (Tamp) carry diagnostic and prognostic information regarding cardiac morbidity and mortality. Heart rate and QT interval are known to be heritable traits. The heritability of T-wave morphology parameters such as TpTe and Tamp is unknown. TpTe and Tamp were evaluated in a large sample of twins. METHODS AND RESULTS: Twins from the GEMINAKAR study (611 pairs, 246 monozygotic, 365 dizygotic; mean age, 38±11 years; 49% men) who had an ECG performed during 1997 to 2000 were included. Tamp was measured in leads V1 and V5. Duration variables (RR interval, QTpeak and QTend interval) were measured and averaged over 3 consecutive beats in lead V5. TpTe was calculated as the QTend- and QTpeak-interval difference. Heritability was assessed using structural equation models adjusting for age, sex, and body mass index. All models were reducible to a model of additive genetics and unique environment. All variables had considerable genetic components. Adjusted heritability estimates were as follows: TpTe, 46%; Tamp lead V1, 34%; Tamp lead V5, 47%; RR interval, 55%; QT interval, 67%; and Bazett-corrected QT interval, 42%. CONCLUSIONS: RR interval, QT interval, Tamp, and TpTe interval are heritable ECG parameters.

Reference values of electrocardiogram repolarization variables in a healthy population.

INTRODUCTION: Reference values for T-wave morphology analysis and evaluation of the relationship with age, sex, and heart rate are lacking in the literature. In this study, we characterized T-wave morphology in a large sample of healthy individuals. METHOD: A total of 1081 healthy subjects (83% men; range, 17-81 years) were included. T-wave morphology variables describing the duration, area, slopes, amplitude, and distribution were calculated using 10-second digital electrocardiogram recordings. Multivariate regression was used to test for dependence of T-wave variables with the subject age, sex, and heart rate. RESULTS: Lead V5 (men vs women) T-wave variables were as follows: amplitude, 444 versus 317 muV; area, 48.4 versus 33.2 ms mV; Tpeak-Tend interval, 94 versus 92 milliseconds; maximal descending slope, -5.15 versus -3.69 muV/ms; skewness, -0.24 versus -0.22; and kurtosis, -0.36 versus -0.35. Tpeak-Tend interval, skewness, and kurtosis were independent of age, sex, and heart rate (r(2) < 0.05), whereas Bazett-corrected QT-interval was more dependent (r(2) = 0.40). CONCLUSION: A selection of T-wave morphology variables is found to be clinically independent of age, sex, and heart rate, including Tpeak-Tend interval, skewness, and kurtosis.