18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study.

PURPOSE: Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. METHODS: We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). RESULTS: In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. CONCLUSIONS: These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG.

Reduced inotropic reserve is predictive of further degradation in left ventricular ejection fraction in patients with Duchenne muscular dystrophy.

AIMS: Duchenne muscular dystrophy (DMD), an inherited X-linked muscular disease, is associated with dilated cardiomyopathy that is responsible for death in 40% of patients. Our objective was to determine whether inotropic reserve is predictive of LV trend over time. METHODS AND RESULTS: A total of 69 DMD patients (age 12.2±2.3 years) were investigated. At baseline, LVEF and the presence of inotropic reserve (defined as an increase in LVEF >10% during dobutamine infusion) were investigated using radionuclide ventriculography. During follow-up (FU), LVEF was remeasured after a mean 29±19 months delay. In the whole population, mean LVEF was 58±8% at baseline and declined to 54±11% during FU (P =0.004). At baseline, 21 patients (30.4%) had LVEF <55% and 38 had no LV inotropic reserve. LVEF declined in the 38 patients (55.1%) without LV inotropic reserve (58±8% to 52±10%, P =0.001), and not in the other patients (58±8% to 57±11%, P =0.516) (P =0.042 for trends in LVEF between groups after adjustment for age, FU duration, and baseline LVEF). Fewer patients with vs. without inotropropic reserve at baseline show a depressed LVEF <55% during follow-up(35.5% vs. 63.2%, respectively, P =0.030). Similar findings were observed in the subgroups of patients with LVEF >45% or 55% at baseline. CONCLUSION: Inotropic reserve assessment allows the distinction of DMD patients who will vs. those who will not show a deterioration in LVEF, thus offering a sensitive approach for delineating the presence and progression of cardiovascular disease in these patients.

Myocardial perfusion imaging in Takayasu arteritis.

OBJECTIVE: Myocardial perfusion defects using scintigraphy have been frequently observed in patients with Takayasu arteritis (TA) without coronary stenosis. The aim of our study was to evaluate coronary microcirculation in TA using thallium-201 (201Tl) myocardial scintigraphy and dipyridamole (DPM) as vasodilator agent. METHODS: Twenty-five consecutive patients with TA were prospectively recruited. They were asymptomatic for cardiac issues and examined using 201Tl myocardial scintigraphy at rest and after coronary artery vasodilation with intravenous DPM. Factors associated with improvement in myocardial perfusion after DPM were identified in patients with TA. RESULTS: Among 25 patients with TA, 21 (84%) had 201Tl myocardial perfusion defects and 4 (16%) had normal resting myocardial perfusion. Using a 17-segments model for quantitative image analysis, DPM significantly improved resting 201Tl myocardial perfusion in 14 patients (61%) versus 9 patients without improvement (39%). We were able to examine coronary artery stenoses in 11 patients, including 10 patients with thallium perfusion defects, and significant coronary artery stenoses were present in only 2 patients (18.2%). No significant difference was found in traditional cardiovascular risk factors between TA patients with or without improvement of myocardial perfusion after DPM. The absence of improvement in myocardial perfusion after DPM tended to be closely associated with specific features and prognostic factors of TA, such as aortic regurgitation at diagnosis, renovascular hypertension, longer duration of TA disease, and male sex. CONCLUSION: We found the significantly high prevalence of myocardial perfusion defects mostly improved after vasodilation with DPM, which may indicate the major role of microcirculatory dysfunction in myocardial ischemia in TA.

Proof of principle for transfusion of in vitro-generated red blood cells.

In vitro RBC production from stem cells could represent an alternative to classic transfusion products. Until now the clinical feasibility of this concept has not been demonstrated. We addressed the question of the capacity of cultured RBCs (cRBCs) to survive in humans. By using a culture protocol permitting erythroid differentiation from peripheral CD34(+) HSC, we generated a homogeneous population of cRBC functional in terms of their deformability, enzyme content, capacity of their hemoglobin to fix/release oxygen, and expression of blood group antigens. We then demonstrated in the nonobese diabetes/severe combined immunodeficiency mouse that cRBC encountered in vivo the conditions necessary for their complete maturation. These data provided the rationale for injecting into one human a homogeneous sample of 10(10) cRBCs generated under good manufacturing practice conditions and labeled with (51)Cr. The level of these cells in the circulation 26 days after injection was between 41% and 63%, which compares favorably with the reported half-life of 28 ± 2 days for native RBCs. Their survival in vivo testifies globally to their quality and functionality. These data establish the proof of principle for transfusion of in vitro-generated RBCs and path the way toward new developments in transfusion medicine. This study is registered at http://www.clinicaltrials.gov as NCT0929266.

Increased serum thyroglobulin levels and negative imaging in thyroid cancer patients: are there sources of benign secretion? A speculative short review.

After thyroidectomy and 131I ablation for differentiated thyroid cancer (DTC), serum thyroglobulin (Tg) became a sensitive marker of residual disease. It is not uncommon to find patients at follow-up with persistent serum Tg levels and no other clinical or imaging evidence for the disease. The vast majority of these patients, most probably, have occult foci of disease, often in minute cervical lymph nodes. A review of the literature including papers published on PubMed/Medline until June 2010 was made. In this study we speculated that a minority of patients who had undergone surgery for differentiated thyroid cancer might have benign sources of Tg secretion at follow-up. These sources may be foci of radio-resistant ectopic thyroid tissue or a thyroid stimulating hormone-stimulated thymus.

In vivo quantification of 18f-fdg uptake in human placenta during early pregnancy.

18F-FDG is the most widely used PET radiopharmaceutical. Nevertheless, no data for 18F-FDG uptake in the human placenta have been reported. We recently reported on embryo dosimetry in a woman who underwent an 18F-FDG PET/CT scan during early pregnancy. In the present work we attempt an in vivo quantification of the 18F-FDG uptake by the placenta. The 27-y-old woman received 320 MBq of 18F-FDG for a follow-up study for Hodgkin's lymphoma and was later discovered to be pregnant (embryo age = 8 wk). Imaging started 1 h after injection. The maximum placental tissue uptake (SUVmax) was 2.5. This value was conservatively attributed to the entire placental volume, i.e., 45 mL, a value representative of the average dimensions of a normal placenta at 8 wk. On the basis of these measurements, placenta 18F-FDG uptake in our patient was 0.19% of the injected activity. A Monte Carlo simulation was used to derive the photon dose to the embryo from the placenta (0.022 x 10(-2) mGy per MBq of injected 18F-FDG) and from the surrounding amniotic fluid (0.017 x 10(-2) mGy MBq(-1)). This increases our previously calculated dose (3.3 x 10(-2) mGy MBq(-1)) by only a small fraction (1.18%), which does not justify modifying the previous estimate given the overall uncertainties.

[123I]-FP-CIT and [99mTc]-HMPAO single photon emission computed tomography in a new sporadic case of rapid-onset dystonia-parkinsonism.

UNLABELLED: Rapid-onset dystonia-parkinsonism (RDP) is a rare, autosomal-dominantly inherited syndrome characterized by abrupt onset, over hours to days, of dystonic and parkinsonian symptoms. To date, RDP has been described in a small number of families, and in only four sporadic cases. METHODS: We here report a new sporadic case of RDP who has a novel de novo mutation in the ATP1A3 gene. Striatal dopamine transporters have been assessed quantitatively using [123I]-FP-CIT SPECT. A volume of interest (VOI) was drawn within the occipital cortex to obtain non-specific activity and specific to non-specific binding ratios (BR) were calculated. A single template of predefined VOI 3D-drawn on right and left caudate nucleus and putamen was applied to the spatially normalized BR images. BR values were compared to those obtained from an age-matched control group and from a group of patients suffering from Parkinson's disease (Hoehn and Yahr score 2 or 3). A [99mTc]-HMPAO cerebral blood flow study was also performed. RESULTS: In the control group, BR values (mean+/-Standard Deviation) were 3.5+/-0.4 for the left striatum and 3.3+/-0.3 for the right one. RDP patient's values were 3 and 2.7, respectively. In the Parkinson group, values were 1.6+/-0.3 and 1.7+/-0.4, respectively. [99mTc]-HMPAO scan showed homogeneous cortical and sub-cortical perfusion. CONCLUSION: Quantification of striatal [123I]-FP-CIT uptake in a new sporadic case of RDP with a novel mutation in the ATP1A3 gene showed values just within the range of normality. [99mTc]-HMPAO scan was normal.

Dopaminergic deficit is not the rule in orthostatic tremor.

Involvement of the dopaminergic system in orthostatic tremor is controversial. The aim of this study was to detect possible dopaminergic denervation in primary orthostatic tremor (OT). Twelve consecutive patients with a firm diagnosis of primary orthostatic tremor were compared with age-matched normal controls. All the patients had a neurological examination, surface polymyography, and quantification of striatal dopamine transporters with (123)I-FP-CIT SPECT imaging. There was no significant difference in (123)I-FP-CIT SPECT findings between controls and patients with OT. Longstanding primary orthostatic tremor is not necessarily associated with (123)I-FP-CIT SPECT abnormalities, as 8 of our patients had more than a 10-year history of OT. Primary orthostatic tremor without dopaminergic denervation remains a valid entity, although representing only a subtype of high-frequency OT. A new role may emerge for (123)I-FP-CIT SPECT in distinguishing between patients whose symptoms will be restricted to OT throughout the disease course and patients at an increased risk of developing PD. (c) 2008 Movement Disorder Society.

Estimation of the beta+ dose to the embryo resulting from 18F-FDG administration during early pregnancy.

UNLABELLED: Although 18F-FDG examinations are widely used, data are lacking on the dose to human embryo tissues in cases of exposure in early pregnancy. Although the photon component can easily be estimated from available data on the pharmacokinetics of 18F-FDG in female organs and from phantom measurements (considering the uterus as the target organ), the intensity of embryo tissue uptake, which is essential for deriving the beta+ dose, is not known. We report the case of a patient who underwent 18F-FDG PET/CT for tumor surveillance and who was later found to have been pregnant at the time of the examination (embryo age, 8 wk). METHODS: The patient received 320 MBq of (18)F-FDG. Imaging started with an unenhanced CT scan 1 h after the injection, followed by PET acquisition. PET images were used to compute the total number of beta+ emissions in embryo tissues per unit of injected activity, from standardized uptake value (SUV) measurements corrected for partial-volume effects. A Monte Carlo track structure code was then used to derive the beta+ self-dose and the beta+ cross-dose from amniotic fluid. The photon and CT doses were added to obtain the final dose received by the embryo. RESULTS: The mean SUV in embryo tissues was 2.7, after correction for the partial-volume effect. The mean corrected SUV of amniotic fluid was 1.1. Monte Carlo simulation showed that the beta+ dose to the embryo (self-dose plus cross-dose from amniotic fluid) was 1.8E-2 mGy per MBq of injected 18F-FDG. Based on MIRD data for the photon dose to the uterus, the estimated photon dose to the embryo was 1.5E-2 mGy/MBq. Thus, the specific 18F-FDG dose to the embryo was 3.3E-2 mGy/MBq (10.6 mGy in this patient). The CT scan added a further 8.3 mGy. CONCLUSION: The dose to the embryo is 3.3E-2 mGy/MBq of 18F-FDG. The beta+ dose contributes 55% of the total dose. This value is higher than previous estimates in late nonhuman-primate pregnancies.

Scintigraphic visualization of glossal thyroid tissue during the follow-up of thyroid cancer patients.

PURPOSE: Nests of thyroid tissue in the tongue are described in about 10% of necropsies. This ectopic thyroid tissue usually lies dormant, but may manifest itself during times of increased stimulation. The aim of our study was to assess the frequency of lingual thyroid visualization on I-131 diagnostic whole-body scan during the follow-up of thyroid cancer patients. MATERIAL AND METHODS: We reviewed the files of 548 consecutive patients who underwent a diagnostic whole-body scan with 200 MBq of I-131 between January 2000 and December 2005, as part of the follow-up for a differentiated thyroid cancer. Every patient had been previously treated with a total thyroidectomy and had received 3.7 GBq (100 mCi) of I-131 for remnant ablation. RESULTS: A focus of uptake located between the 2 submandibular salivary glands, suggestive of ectopic thyroid tissue in the tongue or in the upper part of the thyroglossal duct, was found in 5 of the 548 patients (0.9%). In only one of these patients was the uptake visible at the time of postsurgery thyroid remnant ablation scan. Thyroglobulin (Tg) levels were positive under stimulation in 3 of the 5 patients, and another patient had undetectable Tg, but positive anti-Tg antibodies. Radiologic imaging (MRI and/or ultrasound) was performed in 3 patients and confirmed the presence of a mass suggestive of ectopic thyroid tissue in two. Invasive lingual biopsy was not performed to verify the benign nature. CONCLUSION: When examining whole-body scans (therapeutic or diagnostic) in a patient with persistent Tg detection after thyroid ablation, one should carefully search for any uptake between the submandibular glands that may be suggestive of ectopic tissue.

Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome.

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of (131)I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and (131)I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative (131)I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive (131)I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of (131)I. The bone metastases in the remaining eight patients were discovered on the post-surgery (131)I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to (131)I therapy, with (131)I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused (131)I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite (131)I therapy. Post-surgical (131)I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by (131)I therapy.

Should 'low-risk' thyroid cancer patients with residual thyroglobulin be re-treated with iodine 131?

OBJECTIVE: The American consensus statement on patients with low-risk thyroid cancer, published in 2003, suggests repeat (131)I therapy if the thyroglobulin value is elevated at first follow-up. We evaluated this strategy in our practice. METHODS: Among 407 patients with thyroid cancer who had total thyroidectomy and (131)I ablation between January 2000 and December 2003, 12 patients with stage I thyroid cancer (any tumour (T), any node (N), metastasis (M)0 if < 45 years or T1, N0, M0 if > 45 years), were re-treated on the basis of their thyroglobulin level at first follow-up. Mean patient age was 32.8 years. None of them had a T4 tumour. Thyroglobulin levels after thyroid hormone withdrawal 'off-T4' ranged between 4.5 and 251 ng/ml (median 8). One to four courses of 3.7 GBq (131)I were given. RESULTS: Three patients had a negative (131)I therapy scan and an uneventful course. Two patients had slight residual uptake only in the thyroid bed and negative ultrasound examination. Four patients had isolated (131)I uptake in the mediastinal region. No abnormalities were found on complementary mediastinal imaging. This finding was interpreted as benign (131)I thymic uptake. The last three patients also had mediastinal thymic uptake associated with a slight thyroid bed uptake. One patient had a gradual increase in the thyroglobulin level, and underwent resection of nonfunctioning neck lymph nodes. Thyroglobulin levels declined in all other patients. CONCLUSIONS: No distant lesions were found in a group of young 'low-risk' thyroid cancer patients given empirical (131)I therapy for residual thyroglobulin. When blind (131)I therapy shows no uptake, or uptake limited to the thymus, (131)I therapy should not be repeated. The authors also briefly discuss the hypothesis that enhanced thymus might be a source of benign thyroglobulin secretion.

Stimulation test in the follow-up of thyroid cancer: plasma rhTSH levels are dependent on body weight, not endogenously stimulated TSH values.

BACKGROUND: Stimulation testing in the first year following thyroid ablation has important prognostic value in thyroid cancer patients. Recombinant human TSH (rhTSH) is better tolerated than thyroid hormone withdrawal but provides only transient stimulation so that the TSH threshold of 30 mIU x l(-1) which defines adequate testing during thyroid hormone withdrawal is not appropriate for rhTSH stimulation. We looked at rhTSH levels after a standard two intramuscular injections of 0.9 mg rhTSH. METHODS: Plasma rhTSH levels were measured 24 h after the second injection in 143 consecutive patients. RESULTS: rhTSH levels showed large inter-patient variation (range: 44-240; mean+/-SD: 131+/-48). There was a strong inverse correlation between TSH levels and body weight (P<0.001). Levels lower than 80 mIU x l(-1) (corresponding to 1 SD below average) were recorded in 24 patients (16.8%). These patients had an average body weight of 79.7 kg, as compared to 67.9 kg for those patients with TSH levels higher than 80 mIU x l(-1). A withdrawal test in the first year after thyroid ablation was available in 64 patients. Only one patient (1.6%) had inadequate endogenous TSH stimulation, and there was no dependence of endogenous plasma TSH levels upon weight. CONCLUSION: Contrary to endogenous stimulation, TSH levels after rhTSH injection vary with body weight. The dosage of rhTSH may need to be adapted in patients with more than 80 kg body weight.

Which thyroid cancer patients need periodic stimulation tests?

PURPOSE: Recurrences are frequent in thyroid cancer patients and long-term follow-up is therefore necessary. We evaluated the yield of rhTSH stimulation in three groups of patients, classified according to the UICC/TNM risk stratification and the results of first follow-up testing. METHODS: The study population comprised 129 patients referred for rhTSH testing. All had undergone first follow-up testing after thyroid hormone withdrawal (off-T4) within 1 year of 131I ablation. Negative first follow-up testing was defined as Tg <2 ng/ml and no neck uptake on 131I diagnostic whole-body scan. Seventy-five patients had stage I thyroid cancer and negative first follow-up testing (group A), 19 had stage I disease and positive first follow-up testing (group B), and 35 had stage II-IV disease (group C). RhTSH stimulation was performed an average of 6 years after first follow-up testing. RESULTS: 131I diagnostic scanning after rhTSH was negative in all 75 group A patients. Only one group A patient had detectable Tg after rhTSH injection (1.5 ng/ml), but Tg had also been detected at baseline in this patient (1.45 ng/ml). Given the absence of a response to stimulation, suggesting an interference, Tg was reassessed with a different technique and proved to be undetectable (<0.1 ng/ml). Stimulation with rhTSH in group B showed residual Tg in seven patients and residual 131I uptake in the thyroid bed in two patients, but none of these patients had signs of disease progression. Five group C patients (14%) had a positive rhTSH test result, and this was suggestive of disease progression in at least two cases. CONCLUSION: The first follow-up testing is essential for prognostic classification after 131I ablation of thyroid cancer. In stage I patients, undetectable Tg and negative 131I scan 1 year after ablation define a large population of subjects who have a very low risk of recurrence and who do not require further stimulation tests. In contrast, periodic rhTSH stimulation tests appear useful in higher-risk patients.

[PET in thyroid cancers]. / La TEP dans le cancer de la glande thyroïde.

FDG PET can detect thyroid cancer in patients referred for exploration of a different cancer. Because of its lack of specificity, however, this modality is not indicated for examination of thyroid nodules: ultrasonography and fine needle biopsy with cytology allow histological diagnosis, which can be completed by iodine-123 scintigraphy when an autonomous nodule is suspected. No information is currently available about the utility of FDG PET in preoperative staging. In follow-up of patients undergoing thyroidectomy for adenocarcinoma, FDG PET is useful for detecting recurrence in cases where serum thyroglobulin levels rise and iodine-131 scintigraphy is negative: surgical resection may be appropriate. Nonetheless FDG PET should be performed more widely and earlier: the initial presence of foci positive for FDG is a major predictor of shorter survival, and most cancer lesions take up either iodine or FDG. In follow-up of medullary carcinoma, FDG PET detects residual tissue better than any other scintigraphic procedures, especially when serum levels of CEA (carcinoembryonic antigen) are rising rapidly. FDOPA PET seems to have better sensitivity than FDG-PET and may be useful in occult recurrence, as three case reports indicate.

Psychogenic parkinsonism: a combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy.

We evaluated the concordance between independent clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations as a staged procedure for an accurate diagnosis in 9 patients referred with a diagnosis of suspected psychogenic parkinsonism. Three patients were reclassified as pure psychogenic parkinsonism (PP), 6 with a form of combined psychogenic parkinsonism and Parkinson's disease (PP + PD), and none with pure Parkinson's disease (PD). Electrophysiological recordings showed the characteristics of psychogenic tremor in 5 of 7 patients with tremor. In two of these 5, PD tremor was also recorded. SPECT scan results were abnormal in five of 9 patients. In one case of clinically suspected PP + PD, SPECT scan results were normal. Long-term follow-up supported the final diagnosis of PP (initial clinical misdiagnosis). Electrophysiology contributes to the clinical diagnosis of psychogenic tremor and may help confirm associated organic PD tremor. [(123)I]-FP-CIT SPECT is a robust test to ascertain dopaminergic denervation and increase the confidence of the clinical and electrophysiological diagnosis of associated PD. A combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy in order to distinguish PP from PP + PD.

Myocardial contractility is early affected in systemic sclerosis: a tissue Doppler echocardiography study.

AIMS: Systemic sclerosis (SSc) is a connective tissue disorder characterized by frequent myocardial involvement. Alteration in left ventricular (LV) function is reported to be rare; however, it may be underestimated by conventional measurements. Our aim was to prospectively investigate LV function in SSc patients, using Tissue Doppler echocardiography (TDE), a modern and accurate method of assessing myocardial function. METHODS AND RESULTS: Seventeen consecutive SSc patients with normal cardiac examination, pulmonary artery pressure (PAP) and radionuclide LV ejection fraction (EF) were prospectively investigated. Myocardial perfusion was investigated using single-photon-emission computerized tomography (SPECT). Echocardiography (ECHO), systolic and diastolic strain-rate (SR) measured in the posterior wall by TDE were used to investigate myocardial function, and compared with results of 15 matched controls. All patients (53+/-8 years; 14 women; systolic PAP 33+/-6 mmHg; LVEF 67+/-8%) had myocardial SPECT perfusion abnormalities. Despite normal ECHO, they had lower systolic SR than controls (1.7+/-0.5 versus 3.8+/-1.7 cm-1, p<0.0001), and lower diastolic SR (3.7+/-1.5 versus 5.6+/-1.2 cm-1, p=0.0004). Ten SSc patients had reduced systolic SR<1.7 cm-1 and 11 reduced diastolic SR<3.5 cm-1. CONCLUSION: Frequent abnormal myocardial perfusion is confirmed in SSc patients. Reduced contractility is also frequent as detected by TDE, despite normal radionuclide LVEF.

Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy.

OBJECTIVES: The aim of this research was to examine the effects of perindopril on cardiac function in patients with Duchenne muscular dystrophy (DMD). BACKGROUND: Duchenne muscular dystrophy, an inherited X-linked disease, is characterized by progressive muscle weakness and myocardial involvement. METHODS: In phase I, 57 children with DMD and a left ventricular ejection fraction (LVEF) >55% (mean 65.0 +/- 5.4%), 9.5 to 13 years of age (mean 10.7 +/- 1.2 years), were enrolled in a three-year multicenter, randomized, double-blind trial of perindopril, 2 to 4 mg/day (group 1), versus placebo (group 2). In phase II, all patients received open-label perindopril for 24 more months; LVEF was measured at 0, 36, and 60 months. RESULTS: Phase I was completed by 56 (27 in group 1 and 29 in group 2) and phase II by 51 patients (24 in group 1 and 27 in group 2). There was no difference in baseline characteristics between the treatment groups. At the end of phase I, mean LVEF was 60.7 +/- 7.6% in group 1 versus 64.4 +/- 9.8% in group 2, and was <45% in a single patient in each group (p = NS). At 60 months, LVEF was 58.6 +/- 8.1% in group 1 versus 56.0 +/- 15.5% in group 2 (p = NS). A single patient had an LVEF <45% in group 1 versus eight patients in group 2 (p = 0.02). CONCLUSIONS: Early treatment with perindopril delayed the onset and progression of prominent left ventricle dysfunction in children with DMD.

High prevalence of right ventricular systolic dysfunction in early systemic sclerosis.

OBJECTIVE: To assess right ventricular (RV) function in patients with early systemic sclerosis (SSc) and the acute effects of calcium channel blockers on RV ejection fraction (RVEF). METHODS: Forty-two consecutive patients with SSc with less than 5 years' disease duration and normal pulmonary arterial pressure (35 women, 7 men; mean age 54.3 +/- 9.7 years; 16 with diffuse and 26 with limited cutaneous forms, systolic pulmonary arterial pressure 30.3 +/- 5.4 mmHg) were prospectively evaluated. All underwent pulmonary function testing, echocardiography, and radionuclide ventriculography at rest and 2 hours after receiving 40 mg oral nicardipine, and were compared at baseline with 20 gender and age matched controls. RESULTS: None of the patients with SSc had clinical evidence of heart failure. At baseline, SSc patients had significantly lower LVEF (68.5% +/- 7.9 vs 72.4% +/- 5.0, p = 0.049) and RVEF (36.5% +/- 7.0 vs 45.8% +/- 5.7, p < 0.0001). Sixteen patients had reduced RVEF (< 35%), 3 had reduced LVEF (< 55%), and 10 had reduced peak filling rate (PFR). RVEF correlated to both LVEF and PFR (r = 0.64, p < 0.0001, and r = 0.36, p = 0.0037, respectively), whereas no correlation was found with pulmonary function impairment or pulmonary arterial pressure. Nicardipine resulted in a significant increase in RVEF (from 36.5% +/- 7.0 to 42.3% +/- 8.4, p < 0.001) whereas afterload indicated by mean arterial pressure did not differ significantly. CONCLUSION: Reduced RVEF appears to be a common feature in early SSc; it may be due to intrinsic myocardial involvement and is acutely improved by nicardipine.