Frequency, diagnosis, pathogenesis and management of osteoporosis in alkaptonuria: data analysis from the UK National Alkaptonuria Centre.

Osteoporosis and fractures are common features of alkaptonuria. INTRODUCTION: A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU. METHODS: Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated. RESULTS: Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p < 0.05). CT LS showed an inverse relationship with fractures (R = - 0.28; p < 0.05). CT LS was significantly lower in the fracture group (p < 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p < 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p < 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p < 0.05). CONCLUSIONS: Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.

Correction to: Nuclear medicine services after COVID-19: gearing up back to normality.

The authors P. Orellana and N. El-Haj were inadvertently deleted in the original paper.

Impact of dosing frequency (once daily or twice daily) on patient adherence to oral targeted therapies for hematologic malignancies: a retrospective cohort study among managed care enrollees.

PURPOSE: Existing studies evaluating patient adherence to oral targeted therapies such as tyrosine kinase inhibitors focus on small populations with single malignancies. This study evaluated patterns of use of oral agents in a larger population across multiple hematologic malignancies. METHODS: Adult patients diagnosed with a hematologic malignancy and prescribed oral targeted therapy between 2011 and 2016 (N = 18,976) were identified from the MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Eligible patients were enrolled in monthly prescription plans 6 months before and 12 months after the index date (date of first prescription claim; n = 2442). Multivariable logistic regressions were used to determine predictors of adherence using the medication possession ratio (MPR) and persistence through prescription refill gaps. RESULTS: The overall median adherence was 0.9 (MPR ≥ 80%) and was comparable between once-daily (QD) and twice-daily (BID) groups. Overall, 59% of patients were persistent at 12 months. Patients on QD and BID products did not have any significant differences in adherence (fixed-interval MPR, odds ratio 0.94; 95% confidence interval (CI), 0.75-1.18) or persistence (odds ratio 0.93; 95% CI, 0.75-1.17) 12 months from index. Significant predictors of adherence and persistence included patient age, total inpatient admissions, number of adverse events, and total hospital visits. CONCLUSION: Patient-specific clinical factors, rather than regimen-specific factors, were the main predictors of oral targeted therapy adherence and persistence. Adherence to oral targeted therapies appears to be similar for patients on QD and BID regimens in the real-world setting.

Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre.

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.

The role of PET/CT amyloid Imaging compared with Tc99m-HMPAO SPECT imaging for diagnosing Alzheimer's disease.

BACKGROUND: Imaging such as Tc99m-HMPAO single photon emission computed tomography (SPECT), and positron emission tomography/ computed tomography (PET/CT) amyloid scans are used to aid the diagnosis of Alzheimer's disease (AD). OBJECTIVE: We aimed to correlate the ability of these modalities to differentiate Probable AD and Possible AD using the clinical diagnosis as a gold standard. We also investigated the correlation of severity of amyloid deposit in the brain with the diagnosis of AD. METHODS: A retrospective study of 47 subjects (17 Probable AD and 30 Possible AD) who were referred for PET/CT amyloid scans to our centre was conducted. Hypoperfusion in the temporo-parietal lobes on Tc99m-HMPAO SPECT and loss of grey-white matter contrast in cortical regions on PET/CT Amyloid scans indicating the presence of amyloid ß deposit were qualitatively interpreted as positive for AD. SPECT and PET/CT were also read in combination (Combo reading). The severity of amyloid ß deposit was semiquantitatively assessed in a visual binary method using a scale of Grade 0-4. The severity of amyloid ß deposit was assessed in a visual binary method and a semi-quantitative method using a scale of Grade 0-4. RESULTS: There was significant correlation of Tc99m-HMPAO SPECT, PET/CT amyloid findings and Combo reading with AD. The sensitivity, specificity, PPV and NPV were 87.5%, 73.7%, 58.3% and 93.3% (SPECT); 62.5%, 77.4%, 58.8% and 80.0% (PET/CT) and 87.5%, 84.2%, 70.0% and 30.0% (Combo reading) respectively. The grade of amyloid deposition was not significantly correlated with AD (Spearman's correlation, p=0.687). CONCLUSION: There is an incremental benefit in utilizing PET/CT amyloid imaging in cases with atypical presentation and indeterminate findings on conventional imaging of Alzheimer's disease.

Peptide receptor radionuclide therapy with (90)Y-DOTATATE/(90)Y-DOTATOC in patients with progressive metastatic neuroendocrine tumours: assessment of response, survival and toxicity.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to (90)Y-DOTATOC/(90)Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures. METHODS: A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response (PR), stable disease (SD) or progressive disease (PD), and survival analysed. RESULTS: Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare. CONCLUSION: In patients with progressive metastatic NETs receiving (90)Y-DOTATOC/(90)Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit.

The four-variable modification of diet in renal disease formula underestimates glomerular filtration rate in obese type 2 diabetic individuals with chronic kidney disease.

AIMS/HYPOTHESIS: GFR is commonly estimated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and this forms the basis for classification of chronic kidney disease (CKD). We investigated the effect of obesity on the estimation of glomerular filtration rate in type 2 diabetic participants with CKD. METHODS: We enrolled 111 patients with type 2 diabetes mellitus in different stages of CKD. GFR was measured using (51)Cr-labelled EDTA plasma clearance and was estimated using the four-variable MDRD formula. RESULTS: The bias between estimated and measured GFR was -22.4 (-33.8 to -11.0) p < 0.001 in the obese group compared with -6.04 (-17.6 to -5.5) p = 0.299 in the non-obese group. When GFR was indexed to body surface area of 1.73 m(2), the bias remained significant at -9.4 (-13.4 to -5.4) p < 0.001 in the obese participants. CONCLUSIONS/INTERPRETATION: This study suggests that the four-variable MDRD formula significantly underestimates GFR in obese type 2 diabetic participants with CKD.

Treatment of osteoporotic fractures in alkaptonuria by teriparatide stimulates bone formation and decreases fracture rate - A report of two cases.

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 µg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective.

Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United kingdom.

Because death with a functioning graft remains one of the most important causes of long-term renal transplant failure, cardiac risk stratification and screening for coronary artery disease are essential components of pretransplant assessment. Pretransplant screening for occult coronary artery disease in a subset of these patients may improve outcome. The UK follows the European Best practice guideline 1.5.5 E. Although echocardiography, thallium myocardial perfusion scanning (MPS), dobutamine stress echocardiography, and coronary angiography have been suggested as means of cardiovascular assessment, the best means of assessment remains undetermined. Therefore, we investigated the role of 99m technetium sestamibi myocardial perfusion scanning as an assessment tool for identifying those patients with end-stage renal failure at high risk of cardiovascular death after renal transplantation. Retrospectively, we studied 126 patients that had a MPS as part of their pretransplant assessment. Overall unadjusted survival was 65% at 3 years. Twelve deaths resulted from cardiovascular causes. A reversible defect on MPS was associated with a fatal cardiac event and all-cause mortality. The unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% confidence interval, 1.1 to 18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% confidence interval, 1.1 to 4.4). Thus, MPS may be a useful tool in cardiac risk stratification and in selecting patients with a favorable outcome after renal transplantation. Our patients with a reversible defect in particular have increased cardiac mortality. This group may benefit from coronary angiography.

Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone.

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

The circadian rhythm of osteoprotegerin and its association with parathyroid hormone secretion.

BACKGROUND: Osteoclast resorptive activity, which is known to demonstrate circadian rhythmicity, is regulated by various endocrine hormones and cytokines. PTH suppresses osteoprotegerin (OPG), a regulator of osteoclast activity that has recently been shown to have a circadian rhythm in healthy controls. We studied the differences in the relationship between PTH, OPG, and type I collagen C-telopeptide (betaCTX) over a 24-h period in premenopausal women, elderly postmenopausal women, and elderly men. METHODS: Hourly peripheral venous blood samples were obtained from 18 healthy non-osteoporotic volunteers: premenopausal women (n = 6; mean age, 30.2 +/- 2.2 yr), postmenopausal women (n = 6; mean age, 68.2 +/- 2.6 yr), and elderly men (n = 6; mean age, 68.2 +/- 2.3 yr). Plasma PTH (1-84), OPG, betaCTX, and calcium were measured on all samples. Cosinor analysis was performed to analyze the circadian rhythm parameters. Cross-correlation analysis was used to determine the relationship between the time series of the variables. RESULTS: The 24-h mean PTH, OPG, and betaCTX concentrations were significantly higher in postmenopausal women as compared with premenopausal women and elderly men (P < 0.001). Significant circadian rhythms were observed for PTH (P < 0.05), OPG (P < 0.05), and betaCTX (P < 0.001) in all subjects. PTH secretion was characterized by two peaks in premenopausal women and elderly men and by a sustained increase in PTH concentration in postmenopausal women. OPG secretion was circadian with a daytime increase and nocturnal decrease, and a greater percent decrease in OPG secretion was observed in the postmenopausal women between 1600 and 2400 h. OPG secretion was inversely related to PTH (r = -0.4) and betaCTX (r = -0.6) secretion over a 24-h period. CONCLUSION: This report confirms a circadian rhythm for circulating OPG. The nocturnal decline in circulating OPG is greater in postmenopausal women as compared with premenopausal women and elderly men. Altered PTH secretion may contribute to the OPG secretory pattern in postmenopausal women resulting in increased nocturnal bone resorption.

A JAFROC study of nodule detection performance in CT images of a thorax acquired during PET/CT.

PURPOSE: Two types of CT images (modalities) are acquired in PET/CT: for attenuation correction (AC) and diagnosis. The purpose of the study was to compare nodule detection and localization performance between these two modalities. METHODS: CT images, using both modalities, of an anthropomorphic chest phantom containing zero or more simulated spherical nodules of 5, 8, 10 and 12 mm diameters and contrasts -800, -630 and 100 HU were acquired. An observer performance study using nine observers interpreting 45 normal (zero nodules) images and 47 abnormal images (1-3 nodules; average 1.26) was conducted using the free-response receiver operating characteristic (FROC) paradigm. Data were analysed using an R software package implemented jackknife alternative FROC (JAFROC) analysis. Both empirical areas under the equally weighted AFROC curve (wAFROC) and under the highest rating inferred ROC (HR-ROC) curve were used as figures of merit (FOM). To control the probability of Type I error test alpha was set at 0.05. RESULTS: Nodule detection as measured by either FOM was significantly better on the diagnostic quality images (2nd modality), irrespective of the method of analysis, [reader averaged inter-modality wAFROC FOM difference = -0.07 (-0.11,-0.04); reader averaged inter-modality HR-ROC FOM difference = -0.05 (-0.09, -0.01)]. CONCLUSION: Nodule detection was statistically worse on images acquired for AC; suggesting that images acquired for AC should not be used to evaluate pulmonary pathology.

Surgery for midgut carcinoid.

Many clinicians prefer to avoid surgery in patients with carcinoid neoplasia, because of its slow growth and relatively favourable prognosis. Nevertheless, the commonest cause of death in patients with carcinoid is advanced metastatic disease, and both clinical and epidemiological data indicate that the more effectively the disease is ablated, the more long-lasting the benefit. Multidisciplinary management of patients with carcinoid must consider inherited risk, possible multiple carcinoids and/or synchronous non-carcinoid cancer, and the use of a range of investigations that also evaluate the 10% of patients with carcinoid syndrome with or without valvular heart disease. Although primary size is correlated with the presence of nodal with or without liver metastases, carcinoid tumours <1 cm in diameter may be metastatic at presentation, particularly those arising within the small intestine. In the jejunum and ileum, resection of all sizes of carcinoid with local and regional nodes is preferred, to prevent nodal dissemination causing mesenteric ischaemia with or without infarction. Resection of nodal metastases should be undertaken in those with persistent or recurrent nodal disease if possible. Appendiceal and right colonic carcinoids are most effectively treated by right hemicolectomy with local and regional nodal clearance, as for adenocarcinoma. However, for most appendiceal carcinoids which are <1 cm in diameter and non-invasive, appendicectomy alone is sufficient. For appendiceal carcinoids 1-2 cm in diameter, histopathological assessment helps to determine the need for hemicolectomy. Liver resection has been followed by prolonged 5 year survival in several series and is recommended in appropriate patients to attempt cure or to debulk metastatic disease. Liver transplantation has had only qualified success in highly selected patients without extra-hepatic disease in whom other therapies have failed.

Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection.

AIMS: To determine the sensitivity and specificity of 99mTc-Infecton (Infecton), a novel ciprofloxacin based imaging agent, in detecting sites of infection. METHODS: Ninety patients thought to be suffering from a variety of infections were administered 300-400 MBq of Infecton intravenously. Whole body images were taken one and four hours later. Appropriate specimens were taken for microbiological investigations. Statistical analysis was performed using a computer statistical package. RESULTS: Ninety eight Infecton images were produced. Forty one of these were positive, including three false positives, where the patients had non-infective conditions. Fifty seven negative images were obtained, of which 41 were true negatives and 16 were false negatives, having definite evidence of infection. Thus, Infecton imaging has a sensitivity of 70.3% and a specificity of 93.1% for detecting infective foci. The positive and negative predictive values were 92.6% and 71.9%, respectively. CONCLUSION: Infecton imaging is a new diagnostic tool that is specific for detecting sites of bacterial infection in the body. The high positive predictive value displayed by the technique is clinically important because a positive image strongly supports a diagnosis of bacterial infection. A negative result does not rule out an infection, and may be a result of previous or current antibiotic treatment and/or infection with organisms that do not take up Infecton. Infecton imaging has major advantages over well established imaging techniques, including radiolabelled leucocytes, and may prove to be a superior method for localising bacterial infections.

(131)I-MIBG radionuclide therapy is safe and cost-effective in the control of symptoms of the carcinoid syndrome.

BACKGROUND: The standard treatment used to control the symptoms of carcinoid syndrome (CS) involves subcutaneous injections of the somatostatin analogue octreotide. This is expensive (US $8000--16,000 per year), and treatment may be for many years. The aim of this study was to evaluate the efficacy and cost-effectiveness of our experience over the last 5 years with 1-131-labelled metaiodobenzylguanidine (MIBG) radionuclide therapy in the palliation of patients with CS. METHODS: A consecutive series of 20 symptomatic patients (referred between 1994 and 1999) with CS were evaluated. Fifteen of them underwent(123)I-MIBG scanning. Of the 13 patients with significant tracer uptake in metastatic deposits compared to background, 12 underwent a course of therapeutic(131)I-MIBG (one patient refused). Symptoms, biochemical markers, CT scans, follow-up(123)I-MIBG scans, and the requirement for octreotide were used to assess outcome of treatment. Costs of(131)I-MIBG and octreotide treatments were compared. RESULTS: MIBG treatment was well tolerated in all with only transient side-effects. Ten patients showed a measurable clinical improvement. Seven had a complete clinical response. The mean duration of response was 15.4 months. Octreotide was not required or was reduced in eight patients. Treatment with(131)I-MIBG resulted in a saving of US $1000 per patient, with effective symptom control, when compared to octreotide. CONCLUSION: 1-131 MIBG therapy is a safe and cost-effective therapeutic option to successfully control symptoms in patients with carcinoid syndrome.

The value of ventilation-perfusion imaging in pregnancy.

Pulmonary embolism (PE) is a major cause of maternal death during pregnancy. The aims of this retrospective study were to review 5 years experience of ventilation-perfusion (V/Q) imaging in pregnancy, to evaluate the effect of the V/Q scan report on the referring clinician's use of anticoagulants and to monitor the course and outcome of pregnancy. 82 patients (aged 17-44 years, gestation 6-40 weeks) underwent V/Q imaging for suspected PE, over a 5 year period. Modified PIOPED criteria were used to assess the probability of PE. 31 patients were shown to have normal scans (38%); 19 (23%) had low probability (LP) scans; 14 (17%) had intermediate probability (IP) scans and 18 (22%) had high probability (HP) scans for PE. Referring clinicians saw the reports and took action within 12 h. Anticoagulation was continued or started in 31 patients (all HP, 12 IP and 1 LP). Anticoagulation was considered unnecessary in 52 patients (all normal, 19 LP and 2 IP). None of the patients with normal or LP scans had documented PE during the follow-up period (median 25 months, range 3-60 months). No complications of anticoagulation were observed and no adverse outcome of pregnancy were reported. V/Q imaging is a valuable technique in the management of pregnant women suspected of having PE.

The radiographer and role expansion in nuclear medicine.

With the introduction and wide application of Clinical Governance to all clinical areas, all healthcare professionals including radiographers/technologists working in Nuclear Medicine need to gain skills required for implementation. New professional and legal obligations demand that relevant expertise is developed. This article examines the potential for role expansion of radiographers/technologists in Nuclear Medicine with emphasis on the training and development aspects. The key areas addressed include clinical audit, risk management, research, management and continuing professional development.

Significance of white matter abnormalities in patients with closed head injury.

Neuroimaging in patients with closed head injury (CHI) may frequently reveal abnormalities of white matter. Because white matter abnormalities may be seen in patients aged over 40 years even without CHI, the significance of these abnormalities in patients with CHI is questionable and needs to be assessed in the context of relevance to clinical outcome. The aims of this study were to determine the relative incidence of white matter abnormalities in a group of patients with CHI, and to assess the impact (if any) of these abnormalities on clinical outcome. Sixty-three patients with CHI underwent neuroimaging with magnetic resonance imaging (MRI) and regional cerebral blood flow (rCBF) single photon emission tomography (SPET) approximately 6 months after trauma. Seven patients had white matter abnormalities on MRI scanning. There are no rCBF SPET criteria for defining abnormal perfusion to the white matter. The SPET scans ranged from normal (one patient) and abnormal perfusion to frontal, temporal or parietal lobes in these patients (n = 6). Patients were assessed for outcome after undergoing appropriate rehabilitation programmes with indices of reintegration into the community, activities of daily living, disability, and their cognitive ability to perform tasks. This assessment was conducted 2 years after initial trauma. Of these seven patients with abnormal MRI of the white matter, one performed poorly and six had moderate to good clinical outcome. When individual lobar perfusion is considered, abnormal perfusion to the frontal or temporal lobes was significantly associated with poorer outcome (P < 0.005). In conclusion, white matter abnormalities detected by MRI are frequently associated with cortical perfusion defects identified by SPET (6/7 or 86%). However, when these white matter abnormalities were accompanied by perfusion defects in the frontal and temporal lobes, these were statistically significant in predicting poorer outcome.

Does diastolic function evaluated with radionuclide ventriculography predict mortality, hospitalization and the development of new onset heart failure?

Left ventricular systolic dysfunction (LVSD) in asymptomatic patients is associated with the development of heart failure (HF) and the degree of LVSD predicts prognosis. Whether left ventricular diastolic dysfunction (LVDD) predicts the development of HF or mortality is not known. Our objective was to investigate the predictive value of LVDD evaluated by radionuclide ventriculography (RN). All patients referred for RN during a 12 month period were included. Medical records were reviewed to determine characteristics of the patients at the time of RN and events occurring during a 5 year follow-up. Data from 195 patients were analysed. During the follow-up period 49 patients (25.1%) died, 41 (21.0%) were admitted to hospital and 25 (12.3%) developed HF. An ejection fraction (EF) <40% was associated with mortality (relative risk (RR), 2.04; P=0.001) and hospital admissions (RR, 1.33; P=0.002). Patients who developed subsequent HF had, on average, lower EF at baseline. In a multivariate analysis the lower the EF the more likely patients were to develop new onset HF (odds ratio, 0.92; 95% CI 0.88-0.97; P=0.003). LVDD evaluated with peak filling rate and time to peak filling rate was not associated with any of the outcomes. However, a higher proportion of patients with pre-existing HF at the time of the RN had abnormal LVDD than patients with no HF. LVDD evaluated by RN is associated with symptoms of HF at the time of assessment but is not a good predictor of mortality, hospitalization or new onset HF. EF remains a better predictor of outcomes.