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Background: Patients with chronic intestinal failure (CIF) are at increased risk of developing renal impairment. The aim of this study was to evaluate the occurrence of chronic kidney disease (CKD) in patients dependent on home parenteral nutrition (HPN) and assess risk factors for renal impairment, including patients with all mechanisms of CIF., Methods: This was a cohort study of patients initiated on HPN between March 1, 2015, and March 1, 2020, at a national UK IF Reference Centre. Patients were followed from their first discharge with HPN until HPN cessation or the end of follow-up on December 31, 2021., Results: There were 357 patients included in the analysis. Median follow-up time was 4.7 years. At baseline, >40% of patients had renal impairment, with 15.4% fulfilling the criteria for CKD. Mean estimated glomerular filtration rate (eGFR) decreased significantly during the first year after initiation of HPN from 93.32 ml/min/1.73 m 2 to 86.30 ml/min/1.73 m 2 at the first year of follow-up (P = 0.002), with sequential stabilization of renal function. Increased age at HPN initiation and renal impairment at baseline were associated with decreased eGFR. By the end of follow-up, 6.7% patients developed renal calculi and 26.1% fulfilled the criteria for CKD., Conclusion: This is the largest study of renal function in patients receiving long-term HPN. After the first year following HPN initiation, the rate of decline in eGFR was similar to that expected in the general population. These findings should reassure patients and clinicians that close monitoring of renal function can lead to good outcomes., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Central venous catheter (CVC) complications are frequently reported in patients receiving home parenteral support (HPS). Compromised CVC integrity or breakage is one such issue. Repairing such breakages can potentially avoid costly and risky catheter replacements., Methods: We completed a retrospective descriptive cohort study using a prospectively maintained data set, in a national UK intestinal failure reference center. Repair success, CVC longevity, and catheter-related bloodstream infection (CRBSI) rates after repair were the primary outcome measures., Results: A total of 763 patients received HPS. There were 137 CVC repairs: 115 (84%) tunneled CVCs and 22 peripherally inserted central catheters (PICCs) attempted in 72 patients. Of the 137 attempts at CVC repair, 120 (88%) were deemed to be successful, allowing a median duration of subsequent CVC use of 336 days following repair (range 3-1696 days), which equates to 99,602 catheter days of HPS infusion. Three patients had a CRBSI within 90 days of repair, and patients required admission to the hospital for refeeding on 14 occasions following repair, such that hospitalization was avoided in 103/120 (86%) occasions following successful CVC repair. There was no increase in the recorded rate of CRBSIs in patients undergoing CVC repair compared with the CRBSI rates of all HPS-dependent patients under our care during the study period (0.03 vs 0.344/1000 catheter days, respectively)., Conclusion: This is the largest single-center experience to demonstrate that CVCs, including PICCs, used for the administration of HPS can be safely repaired, prolonging CVC longevity without leading to an increased risk of CRBSI., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Background: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD)., Objectives: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD., Methods: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information., Results: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT., Conclusions: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT., Competing Interests: Funding Support and Author Disclosures Funding was provided by Bayer AG, Siemens Healthineers, and in part by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. Dr Arai had a Cooperative Research and Development Agreement (CRADA) with Bayer, Siemens, and Circle CVI Inc; and has patents and invention reports related to perfusion quantification and cine MRI. Dr Schulz-Menger has served as an advisor for Bayer. Dr Berman has served as a consultant for Bayer. Dr Han has received research grants from Gilead Sciences and General Electric; has served as a consultant for Acceleron, Bracco, and Complexa; and has served on the Speakers Bureau of General Electric, all unrelated to this work. Dr Gutberlet has received speaker honorarium from Bayer, Bracco, Circle CVI, Philips, and Siemens. Dr Woodard has received research support from Bayer, Lilly, and Roche; had a research agreement with Siemens; and has served as a consultant for Medtronic. Dr Carr has received institutional research grants from Siemens, Bayer, and Guerbet; has received speaker honoraria from Bayer and Guerbet; and has received served on advisory boards of Siemens, Bayer, and Bracco. Dr Friedrich has received grants and personal fees from Circle Cardiovascular Imaging Inc, outside of the submitted work. Drs. Haverstock, Liu, Brueggenwerth, and Santiuste were employees of Bayer. Dr Pennell has received research support from Siemens, ApoPharma Apotex, La Jolla, and Bayer; and has served as a consultant for Apotex, La Jolla, and Bayer. All other authors have reported that they had no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: Chronic analgesic use is described in home parenteral nutrition (HPN)-dependent patients, but there are limited data on factors associated with opioid use for noncancerous pain., Methods: Patients attending a national UK intestinal failure reference center were divided in two groups according to strong opioid (SO) usage; risk factors for SO usage were analyzed using logistic regression., Results: A total of 168 HPN-dependent patients were included. During the study period, 73 patients (43.5%) had documented SO usage (SO group), whereas the remainder did not (No-SO group). The prevalence of Crohn's disease among the No-SO group was twofold higher than among the SO group (43.2% vs 24.7%; P = 0.013), whereas those with surgical complications were twice as prevalent among the SO group (19.2% vs 8.4%, respectively; P = 0.04). The rate of working-age unemployment was significantly higher in the SO group (90.6%) than the No-SO group (55.6%; P = 0.001). Multivariate regression showed unemployment as an independent risk factor for SO usage (OR, 6.005; 95% CI, 1.435-25.134), whereas Crohn's disease (OR, 0.284; 95% CI, 0.09-0.898) and <4 intravenous support (IVS) nights per week (OR, 0.113; 95% CI, 0.012-1.009) were protective factors. The life-long incidence of catheter-related bloodstream infection (CRBSI) was comparable between groups (34.2% SO vs 27.4% No-SO; P = 0.336)., Conclusion: SO use is frequent among HPN-dependent patients and associated with high rates of unemployment and ≥4 IVS nights per week, but not with increased rate of CRBSI. The reduced usage among patients with Crohn's disease warrants further evaluation but might be due to the chronicity as compared with other IF etiologies., (© 2022 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background & Aims: Hepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography., Methods: We conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles., Results: Of 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09-2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18-1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm 3 vs Q1: 414 mm 3 , p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed., Conclusions: Hepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis., Clinical Trial Number: N/A., Competing Interests: Declaration of competing interest GD reports paid lectures from AstraZeneca, Pfizer and Amgen not related to the topic in the manuscript, received conference support from Boehringer Ingelheim and provides consultancy services and has equity interest in Artrya Ltd. NSRL has received research funding and speaker honoraria from Sanofi and conference support from Boehringer Ingelheim. GFW has received financial support for lectures, advisory boards or research from Arrowhead, Amgen, Pfizer, Sanofi, Regeneron, Novartis, AstraZeneca, Silence Therapeutics and Esperion. GFW is a member of the editorial board for Metabolism: Clinical and Experimental. OTA provides consultancy services to Resonance Health and Sun Pharmaceuticals. Khurram Nasir and Raul Santos are colleagues within the field and represent conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: A fungal-related catheter-related bloodstream infection (CRBSI) is less frequent than those induced by bacteria. In the past, a single episode of fungal CRBSI has been used as a marker of home parenteral nutrition (HPN) failure and thus a possible indication for intestinal transplantation., Methods: Survival outcomes were assessed from a prospectively maintained database of patients initiated on HPN for underlying chronic intestinal failure between 1993 and 2018, with a censoring date of December 31, 2020. Cox regression was performed to assess predictors of mortality with univariable and multivariable analysis., Results: A total of 1008 patients were included in the study, with a total of 1 364 595 catheter days. There were 513 CRBSI events recorded in 262 patients, equating to a CRBSI rate of 0.38/1000 catheter days. A total of 38/262 (14.5%) patients had at least one episode of fungal CRBSI, whereas 216/262 (82.4%) had at least one bacterial but no fungal CRBSI. The median time between HPN initiation and the first CRBSI episode was 20.6 months (95% confidence interval, 16.5-24.1). Episodes of fungal or bacterial CRBSI and the number of CRBSI episodes were not associated with increased mortality. Overall, 15 CRBSI-related deaths were observed in the observation period (0.01 CRBSI deaths/1000 catheter days), two of these were fungal in origin., Conclusion: The occurrence of a fungal CRBSI does not increase the risk of death compared with patients who have bacterial CRBSI or those without a CRBSI event., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Background & Aims: Long term outcomes have been reported in home parenteral nutrition (HPN)-dependent patients with type 3 intestinal failure (IF), but there are limited survival data standardised to the general population that would help provide a meaningful prognosis for patients and clinicians. The primary aim of this study was therefore to investigate the survival of HPN-dependent patients and to evaluate the specific impact of type 3 IF on their life expectancy standardised to that of the general population., Methods: This was a cohort study of adult patients initiated on HPN between 1978 and 2018 at a national UK IF reference centre and followed up until death or censoring date of 31st December 2020. The standardised mortality ratio (SMR) was calculated as observed deaths divided by expected deaths using UK Office for National Statistics database. Excess Life Years Lost (LYL) were calculated separately for each sex as the differences in average life expectancy between patients with type 3 IF and the general population. Survival data were evaluated using cox regression models adjusting for confounding., Results: In total, 1046 patients were identified, with a total observation time of 7344.1 patient-years. Patients with malignancy (n = 206) were excluded from the survival analysis. Of the remaining 840 patients, 398 were alive by the end of follow-up. The probability of survival was 91.8% at 1 year, 69.3% at 5 years, 54.3% at 10 years, 29.8% at 20 years and 16.7% at 30 years. Patients who did not achieve nutritional autonomy had an increased likelihood of death compared to patients who ceased HPN. In total, 40 (9.0%) deaths were HPN or IF-related, while underlying disease leading to IF accounted for 98 (22.2%) deaths. There were 270 (61.1%) deaths not related to IF, with the majority of these patients dying from infections unrelated to HPN. Overall mortality rates were higher among patients with a diagnosis of type 3 IF compared with the general UK population with a SMR of 7.48 (95% CI 6.80 to 8.21) and an excess mortality rate of 54.0 per 1000 person-years. All mechanisms of IF were associated with excess mortality, with SMR ranging from 6.82 (95% CI 5.98 to 7.72) for short bowel syndrome to 15.51 (95% CI 11.73 to 20.03) for dysmotility. On average, the excess LYL was 17.45 years for males and 17.39 years for females compared with the general population of the same age., Conclusion: This the largest single-centre series reporting survival outcomes in patients with type 3 IF over more than a four-decade period and the first to report LYL in this patient cohort. Type 3 IF was associated with more than seven-fold higher mortality rates than for the general UK population and shorter life expectancies of more than 17 years. Survival, however, was better in those able to achieve nutritional autonomy. Since the majority of deaths were due to non-HPN or non-IF causes, there is clearly a need now to further explore these causes of death in order to improve our understanding of excessive mortality in type 3 IF and develop ways to prevent it., Competing Interests: Conflict of interest No conflict of interest to declare., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Although international guidelines support the use of commercially available multichamber bags (MCBs), the majority of home parenteral nutrition (HPN) in the United Kingdom has been compounded PN, tailored to the patient. However, national capacity limitations in aseptic facilities have necessitated the increased use of MCBs. There are no studies evaluating the appropriateness or benefits of using a "hybrid" regimen incorporating both MCBs and compounded PN in patients already established on compounded HPN., Methods: This was a cross-sectional audit evaluation conducted on September 1, 2021, at a national United Kingdom reference center. All HPN-dependent adults prescribed HPN for chronic intestinal failure were assessed by a multidisciplinary team for their potential of being switched to a "hybrid" regimen of MCBs and compounded PN., Results: Of 180 patients currently receiving compounded HPN that included intravenous nitrogen with glucose ± lipid, 65 (36.1%) were deemed clinically suitable for a hybrid PN regimen, with minimal variance in PN constituents per week (volume 0%, non-nitrogen kilocalories 0%, nitrogen 0%, fat -0.2%, glucose 0%, sodium 0%, potassium 0%, calcium 0%, magnesium 0%, and phosphate -0.1%) and requiring no additional central venous catheter manipulations. The potential reduction in compounded PN would reduce by 3627 bags per year, equating to a cost saving of £141,453 per year (equivalent to $178,885)., Conclusion: Wider use of hybrid MCB/compounded HPN regimens could lead to a reduction in the need for compounded PN to be produced by aseptic facilities. Further evaluation of acceptability and tolerance of hybrid regimens by patients already receiving compounded HPN is required., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Introduction: Catheter-related bloodstream infections (CRBSIs) remain the commonest complication associated with home parenteral nutrition (HPN). Although the management outcomes of CRBSIs have been extensively reported by specialized intestinal failure (IF) centers, there are minimal data reporting CRBSI outcomes for HPN-dependent patients admitted to nonspecialized hospitals., Method: This was an observational study from a prospectively maintained database of CRBSIs in HPN-dependent patients managed outside of a specialized IF center., Results: Three hundred and six patients from a total cohort of 1066 HPN-dependent patients suffered from 489 CRBSI events from 2003 to 2021; after 2017, 71 of these events were managed at the patient's local, nonspecialized hospital and the remainder at the specialized IF center. From 2017 to 2021, salvage of the central venous catheter (CVC) with antimicrobial therapy was attempted in 32 out of 71 (45.1%) patients admitted to the nonspecialized hospital, with successful salvage recorded in 23 (71.8%) cases. Notably, CVC salvage was attempted more commonly (77 out of 103 [74.8%]; P = 0.004 vs nonspecialized hospital), with a better salvage success rate (64 out of 77 [83.1%] P = 0.01 vs nonspecialized hospital) in patients who were admitted to the specialized IF center., Conclusion: In some instances, CRBSIs can be effectively managed when patients presenting to a nonspecialized hospital; however, overall salvage is more likely to be successful in the specialized setting. Further development of clinical and educational networks between IF centers and patients' local hospitals aimed at standardizing care may lead to improved CRBSI outcomes., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010-2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area. A total of 126 patients were included, with a median distance between the patient's home and the IF center of 17.5 km (IQR 10.9-39.1; maximum 317.4 km). A total of 28 (22%) patients experienced at least one HPN-related complication, the most common being a central venous catheter (CVC) occlusion and electrolyte abnormalities. The catheter-related bloodstream infection (CRBSI) rate was 0.49/1000 catheter days. The CVC type, administration of concomitant chemotherapy via a distinct CVC lumen separate from PN, venting gastrostomy and distance between the patient's home and the IF center were not associated with CRBSI or mechanical CVC complications. A total of 82 (65.1%) patients were readmitted while on HPN, but only 7 (8.5%) of these readmissions were HPN-related. A total of 44 (34.9%) patients died at home, 41 (32.5%) at a hospice and 41 (32.5%) in a hospital. In conclusion, this study demonstrates that a centralized approach to IF care can provide HPN to patients over a large geographical area while maintaining low HPN-related complications that are comparable to patients requiring HPN for benign conditions and low hospital readmission rates., Competing Interests: The authors declare no conflict of interest.

Short bowel syndrome (SBS) and enterocutaneous or enteroatmospheric fistulas are common indications for home parenteral nutrition (HPN). However, there are few data describing factors influencing surgical decision-making or outcomes particularly following fistula development. We aimed to compare outcomes between patients with SBS and fistulas and explore surgical decision-making. HPN-dependent adults from 2001−2018 at a national reference centre were included in this study. HPN cessation was analysed using death as competing risk. In total, 465 patients (SBS (62%), fistula (38%)) were included, with median HPN dependency of 2.6 years. In total, 203 patients underwent reconstructive surgery; while frailty was the commonest reason for not undergoing surgery (49.2%), 22.7% declined surgery. Overall, 170 ceased HPN, with a probability of 13.8%, 34.1% and 38.3% at 1, 5 and 10 years, respectively. Patients undergoing surgery had higher nutritional autonomy rates (109.8 incidences/1000 patient years) compared to those not undergoing surgery (18.1 incidences/1000 patient years; p < 0.001). A total of 295 patients (63.4%) were predicted to cease HPN based on gastrointestinal anatomy but only 162/295 (54.9%) achieved this; those unable to do so were older with a higher comorbidity index. There were no differences in long-term nutritional and survival outcomes or surgical decisions between patients with SBS and fistulas, or between enterocutaneous and enteroatmospheric fistulas. This study represents one of the largest datasets describing the ability of HPN-dependent patients with SBS or fistulas to achieve nutritional autonomy. While reconstructive surgery facilitates HPN cessation, approximately one-fifth of patients declined surgery despite HPN dependency. These data will better inform patient expectation and help plan alternative therapies.

Background: Home parenteral nutrition (HPN) is a life-saving therapy for patients with chronic intestinal failure but can be associated with a degree of psychological distress. The factors associated with the need for antidepressants (ADs) in this cohort have not yet been described., Methods: The study involved prospective data collection from patients attending an HPN clinic at a national intestinal failure referral center. Patients requiring HPN as a result of active malignancy were excluded. Patients were divided in 2 groups according to AD usage; demographic, anthropometric, socioeconomic characteristics, and intravenous supplementation (IVS) regimens were compared between groups., Results: A total of 184 patients were recruited between July 2018 and April 2019, with an overall prevalence of AD use of 41.7% (70/168 patients). Daily mean IVS volume was significantly higher among patients taking AD ("AD" group; 2125.48 ± 991.8 ml/day, "no-AD" group; 1828.54 ± 847.0 ml/day, P = .039), with the proportion of patients needing high-volume IVS (≥3000 ml/day) being 3 times higher in the AD group (20.0%(14/70 patients) vs 6.1% (6/98 patients), P = .006). The average energy IVS infusion per day was similar between the groups., Conclusion: This is the first study to demonstrate that AD use correlates with higher IVS volume rather than energy requirements in HPN patients, suggesting that high IVS volume requirements may be better associated with the patient's disease burden. Early and tailored mental health intervention may be beneficial in those with high IVS volume requirements., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: The risk of bloodstream infections may be increased in hospitalized patients receiving ready-made parenteral nutrition (PN) multichamber bags (MCBs) compared with customized PN; however, as highlighted in recent international guidelines, there are no comparable data relating to home PN (HPN)., Methods: Data from a prospectively maintained database were analyzed to compare incidence rates of catheter-related bloodstream infections (CRBSIs) between patients receiving customized HPN compared with MCB HPN at a national UK referral center between May 2018 and August 2020., Results: Sixty patients with chronic intestinal failure were commenced on MCBs and 45 received customized HPN for a total of 5914 and 7641 catheter days, respectively. No difference in CRBSI incidence was found (0.51/1000 catheter days for MCBs, 0.39/1000 catheter days for customized HPN; incidence rate ratio, 1.29; 95% CI, 0.26-6.37). Eighteen patients were switched from customized HPN to MCB HPN. The study period covered 7401 catheter days receiving customized HPN and 4834 days on MCBs. No significant change was noted in the CRBSI rates following this switch (0.27/1000 catheter days receiving customized HPN vs 0.21/1000 catheter days on MCBs; incidence rate ratio, 1.31; 95% CI, 0.12-14.3)., Conclusion: The use of MCBs for HPN patients is not associated with an increased risk of CRBSI. This study will inform international guidelines and provide reassurance for the continued, safe use of MCB HPN., (© 2021 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background and Aims: Patients with short bowel syndrome and type 3 intestinal failure (SBS-IF) are dependent on parenteral nutrition (PN), a lifesaving treatment but inconvenient and with risks. Glucagon-like peptide 2 analogue (teduglutide) can reduce patients' need for PN. However, it comes with the risk of a number of side effects. This qualitative study investigated patients' decision making process to start teduglutide and how family members contributed to the decision., Methods: In-depth semi-structured interviews were conducted with nine participants, six patients with SBS-IF and three family members about the decision to take teduglutide. Interviews were transcribed verbatim and analysed using framework analysis., Results: The prominent motivation for taking teduglutide (Revestive® Takeda Pharmaceuticals Limited) was reducing or stopping PN. Other motivations were to help others by assisting in developing the knowledge base around teduglutide, patients felt that they had nothing to lose by trying the drug and the support of relatives. The reasons patients considered not taking the drug were that they had accepted being on PN, the potential side effects of teduglutide and undergoing extra monitoring. However, the monitoring programme also acted as a motivator providing reassurance that patients would be observed and supported with side effects. Family members were happy to support patients' decision to try teduglutide, although they had more reservations, indicating a higher risk threshold., Conclusion: Patients considered potential benefits of teduglutide outweighed any disadvantages. Relatives, although supportive, had more reservations., Competing Interests: Declaration of competing interest All the authors report an investigator initiated grant from Takeda into the departments of the intestinal failure unit Salford Royal Foundation Trust and School of Health Sciences, University of Manchester during the conduct of the study and a further grant from Takeda into these departments outside the submitted work. The authors declare a grant from Baxter into the intestinal unit Salford Royal Foundation Trust outside of the submitted work. SL declares personal fees from VectivBio, personal fees from Zealand Pharma, personal fees from Takeda, personal fees from Baxter, personal fees from Fresenius Kabi, outside the submitted work. AMS declares personal fees from Frensus Kabi and expenses from National Nurses Nutrition Group outside the submitted work. AA declares expenses from BBraun outside the submitted work. GL declares expenses from Baxter and BBraun outside the submitted work. KF declares personal fees from Takeda and Shire outside of the submitted work., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Antidepressant drugs, which are widely used in palliative care patients for both management of psychiatric disorders and non-psychiatric symptoms, may cause a cluster of distressing symptoms on discontinuation. In dying patients, cessation of oral intake may occur either temporarily or permanently for reasons related to disease or its treatment, as well as in the days before death. We examined antidepressant use in palliative care patients by risk of antidepressant discontinuation syndrome (ADDS). Strategies for reducing the risk of ADDS, and for managing it that should occur, are discussed., (© 2021 Royal Australasian College of Physicians.)

Background: Infective endocarditis (IE) is a recognized complication of central line-associated bloodstream infection (CLABSI). Central venous access devices (CVADs) are essential for the delivery of long-term parenteral nutrition (PN), yet there are no published data as to the prevalence, characteristics and outcomes of IE in this population., Methods: A prospectively maintained database of patients with intestinal failure (IF) types 2 and 3, managed by a national intestinal failure center between January 2010 and December 2018, was analyzed retrospectively and relevant factors extracted from case records., Results: A total of 745 patients with IF and CVADs in situ on admission, or placed during their stay, were admitted over the duration of this study, 640 with type 2 IF and 105 with type 3 IF. Two hundred eighty-two echocardiograms were performed to investigate potential IE associated with a CLABSI event. Four cases of IE were identified in the entire cohort of 782,666 catheter days (IE incidence rate: 0.005 per 1000 catheter days and 187 per 100,000 person-years for the entire cohort; 0.048 per 1000 inpatient catheter days for acute type 2 IF, 0.0026 per 1000 outpatient catheter days [ie, 99 per 100,000 person-years for outpatients with type 3 IF])., Conclusion: IE is rare in the type 3 IF population and a rare consequence of CLABSI in inpatient acute type 2 IF. However, mortality and morbidity are high. Routine echocardiography may not be warranted for investigation of CLABSI unless there is a high risk of IE or a virulent organism is involved., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Background and Aims: Intestinal failure [IF] is a feared complication of Crohn's disease [CD]. Although cumulative loss of small bowel due to bowel resections is thought to be the dominant cause, the causes and outcomes have not been reported., Methods: Consecutive adult patients referred to a national intestinal failure unit over 2000-2018 with a diagnosis of CD, and subsequently treated with parenteral nutrition during at least 12 months, were included in this longitudinal cohort study. Data were extracted from a prospective institutional clinical database and patient records., Results: A total of 121 patients were included. Of these, 62 [51%] of patients developed IF as a consequence of abdominal sepsis complicating abdominal surgery; small bowel resection, primary disease activity, and proximal stoma were less common causes [31%, 12%, and 6%, respectively]. Further, 32 had perianastomotic sepsis, and 15 of those had documented risk factors for anastomotic dehiscence. On Kaplan-Meier analysis, 40% of all patients regained nutritional autonomy within 10 years and none did subsequently; 14% of patients developed intestinal failure-associated liver disease. On Kaplan-Meier analysis, projected mean age of death was 74 years.2., Conclusions: IF is a severe complication of CD, with 60% of patients permanently dependent on parenteral nutrition. The most frequent event leading directly to IF was a septic complication following abdominal surgery, in many cases following intestinal anastomosis in the presence of significant risk factors for anastomotic dehiscence. A reduced need for abdominal surgery, an increased awareness of perioperative risk factors, and structured pre-operative optimisation may reduce the incidence of IF in CD., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies., Objectives: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging., Methods: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD., Results: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2., Conclusions: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD., (Published by Elsevier Inc.)

Background & Aims: A retrospective evaluation was undertaken in intestinal failure (IF) patients with long term CVCs to evaluate differential time to positivity (DTP) against paired quantitative blood cultures (PP) for the diagnosis of CRBSI., Methods: A list of patients with a diagnosis of CRBSI was obtained from the intestinal failure unit database for a five year period, 2013 to 2017. Microbiology records were reviewed to obtain further information about blood culture and pour plate examinations. Organisms and times of collection, loading and positivity were recorded. Patients with a contemporaneous set of central and peripheral PP and blood cultures were included in an analysis of the sensitivity of DTP compared to PP., Results: There were 61 (45.5%) episodes in 56 patients where complete sets of central and peripheral blood cultures and PP were received. All 61 episodes had positive central blood cultures, 59 (96.7%) had positive central line PP and 17 (27.9%) had positive peripheral PP. Using PP as the gold standard, DTP sensitivity was 96.0% for 50 episodes where PP were consistent with CRBSI. Sensitivity increased to 100% for 17 episodes where there were no delays in either collection or loading of blood cultures., Conclusions: This is the first evaluation to support the use of DTP as a sensitive test in diagnosing CRBSI in patients with IF and provides confidence to IF centers where pour plate cultures are not available., Competing Interests: Conflict of interest The authors declare no conflict of interest. The results presented in this paper have not been published previously., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aims: Familial hypercholesterolaemia (FH) is characterised by a high, but variable risk of premature coronary artery disease (CAD). Cardiac computed tomography angiography (CCTA) can be employed to assess subclinical coronary atherosclerosis. We investigated the features and distribution of coronary artery plaques in asymptomatic patients with and without genetically confirmed heterozygous FH., Methods: We undertook an aged-matched case-control study of asymptomatic phenotypic FH patients with (cases, M+) and without (controls, M-) an FH-causing mutation. Coronary atherosclerosis was assessed by CCTA and calcium scoring. Coronary segments were evaluated for global and vessel-level coronary plaques and degree of stenosis., Results: We studied 104 cases and 104 controls (mean age 49.9 ± 10.4 years), who had a similar spectrum of non-cardiovascular risk factors. Pre-treatment plasma LDL-cholesterol was higher in the M+ than M- group (7.8 ± 2.1 vs 6.2 ± 1.2 mmol/L, p<0.001). There was a greater proportion of patients with mixed and calcified plaque, as well as a higher coronary artery calcium score and segment stenosis score (all p<0.05), in the M+ compared with the M- group. M+ patients also had a significantly higher frequency of coronary artery calcium in the left main and anterior descending and right coronary arteries (all p<0.05), but not in the left circumflex., Conclusions: Among patients with phenotypic FH, those with a genetically confirmed diagnosis had a higher frequency and severity of coronary atherosclerotic plaques, and specifically more advanced calcified plaques., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GFW has received honoraria for advisory boards and research grants from Amgen, Sanofi and Regeneron. The other authors have nothing to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Our intestinal failure unit provides care for patients from a wide geographical area. Patients dependent on home parenteral nutrition (HPN) are routinely reviewed in the clinic at 3-6 monthly intervals. Between March 2008 and 2015, we noted a significant rise in the number of patients under our care, with an associated 51% increase in clinic appointments offered. We evaluated whether telemedicine would provide a strategy to reduce patients' need to travel while maintaining safe clinical standards., Methods: Implementation began in December 2015 via patient consultation and small tests of change. Clinical data were obtained from a prospectively maintained database. Remote video consultation discussions were carried out via internet video call service (Skype). An anonymous satisfaction questionnaire was offered to patients for completion following consultation. The number of miles saved by obviating the need to attend hospital was calculated for each patient., Results: During the study period, patients receiving HPN rose by 18% to 288. Twenty-five patients used telemedicine for HPN follow-up, three of these for follow-up with the psychologist. By avoiding hospital attendance, this saved a mean travel distance of 56.7 miles with a total of 18 346.6 cumulative miles saved. Sixty-three per cent of patients rated their satisfaction with the system at ≥90%, with a mean satisfaction of 85%. Eight per cent of the telemedicine cohort was admitted with an HPN complication, compared with an admission rate of 24% for the whole HPN cohort. One emergency admission was avoided., Conclusion: Telemedicine can obviate the need for clinic attendance in HPN-dependent patients, so reducing the need of individuals with chronic illness to travel while maintaining standards for follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Home parenteral nutrition (HPN) provides fluid and nutrition essential for the survival of patients with type 3 intestinal failure (IF). However, it is associated with complications and re-admission to hospital. This study aims to investigate the effect of HPN on mortality, morbidity and hospital re-admissions., Method: This is a retrospective cohort study. All patients newly dependent on HPN discharged over a 4-year period between 2011 and 2015 were included. Patients' characteristics, nutritional status and diagnosis were recorded, along with frequency and duration of HPN administration. Outcomes collected included hospital re-admissions, morbidity, catheter related blood stream infections (CRBSIs) and mortality. Regression analyses were performed to estimate the rate of different outcomes adjusted for prognostic factors., Results: There were 210 patients included, 561 separate HPN prescriptions equating to 110,537 catheter days. Total number of deaths was 44 (0.398 deaths per 1000 catheter days). There were 196 re-admissions to hospital recorded for a total of 5594 days, 69 (33%) of these re-admissions were unplanned (2484 days in hospital). Principle reasons for unplanned re-admissions included: CRBSIs (n = 31, 45%); other sepsis (n = 10, 14.5%) and abdominal symptoms (n = 9, 13%). CRBSIs were recorded in 22 (10%) patients, equating to a rate of 0.199 per 1000 catheter days. Days per week on HPN increased the relative rate (RR) of time in hospital due to any reason or for unplanned readmissions, RR 1.50 (95% CI: 1.26, 1,78 p < 0.001) and RR 1.39 (95% CI: 1.10, 1.75 p = 0.006) respectively. However, there was no association between days per week on HPN and CRBSI occurrence., Conclusion: Unplanned re-admissions for patients with IF accounted for a third of all hospitalisations in those on HPN and the majority were due to CRBSI. The number of HPN dependent days per week was related to all-cause unplanned re-admissions, although not to CRBSI rate., (Copyright © 2018 European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Severe gastrointestinal dysmotility (GID) is a significant cause of chronic intestinal failure (CIF) with unclear benefits of sub-classifying into Chronic Intestinal Pseudo-obstruction (CIPO) and non-CIPO sub-types. We compared outcomes between CIPO and non-CIPO sub-types in a tertiary cohort of patients with CIF resulting from severe GID., Methods: Adults with primary GID, commenced on home parenteral nutrition (HPN) over a 16-year period at a national referral centre, were included. All patients satisfied GID clinical criteria which mandated evidence of small bowel involvement either objectively (abnormal antroduodenal manometry) or pragmatically (failure to progress on small bowel feeding). Clinical outcomes including HPN dependency and survival were compared between CIPO and non-CIPO sub-types., Results: Patients with primary GID requiring HPN (n = 45, age 38 ± 2, 33 females, 23/45 (51%) CIPO, 22/45 (49%) non-CIPO) were included. Patients with CIPO had more surgical interventions (P = 0.03), higher incidence of bacterial overgrowth (P = 0.006), greater parenteral energy (P = 0.02) and volume requirements (P = 0.05). Overall, during a mean 6 years' follow-up, 36/45 (80%) patients remained HPN dependent. Multivariate analyses confirmed that the non-CIPO sub-type (P = 0.04) and catheter related blood stream infections/1000 days (P = 0.01) were predictive factors for time to discontinuing HPN. Overall 5-year survival on HPN was 85%, with no difference between sub-types (P = 0.83)., Conclusions: The CIPO sub-type is associated with higher HPN dependency and should be recognized as a separate entity in severe GID. In multidisciplinary settings with continuous close monitoring of risks and benefits, our data confirm HPN is a safe, life-preserving therapy in severe GID related CIF., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: There are minimal reports of pregnancy in the chronic intestinal failure (CIF)/ home parenteral nutrition (HPN) population, with some concern relating to the risk associated with such pregnancies. The aim of this retrospective observational study was to evaluate pregnancy experience and outcomes in patients with CIF requiring HPN in a national UK CIF referral centre., Method: All known pregnancies in patients treated with HPN for CIF between 1982 and 2016 were identified retrospectively from a prospectively maintained database. Maternal and foetal outcomes were collated, along with PN requirements before and during pregnancy., Results: There were 5 pregnancies in 5 mothers in our cohort consisting of over 700 patients, males and females. The median age at conception was 28 years (range 24-33 years). The median duration on HPN prior to pregnancy was 26 months (range 4-85 months). One patient had Crohn's disease, another had pan-enteric dysmotility and the other three patients had ischaemic complications leading to short bowel syndrome (SBS). All mothers were intensively monitored in an obstetric clinic and a dedicated CIF multi-disciplinary clinic throughout pregnancy. There were 2/5 preterm deliveries. One of the preterm deliveries was associated with spontaneous labour and the other had a planned induction as a result of maternal clinical need. Neonatal complications were seen in both prenates. There were no recorded maternal catheter related line infections during the 5 pregnancies., Conclusion: Successful pregnancy whilst receiving HPN is feasible but requires close, intensive monitoring and dedicated optimisation of PN in order to minimise maternal and foetal complications. All women of child-bearing age on HPN should be counselled about pregnancy.

Background: Home parenteral nutrition (HPN) is the mainstay of treatment for patients with Type 3 intestinal failure (IF), however long term data on mortality and nutritional outcomes are limited., Objectives: To assess the long-term survival and requirements for ongoing HPN in patients receiving treatment at a UK national referral centre for intestinal failure., Methods: Patients with IF who received HPN for more than 3 months at this Intestinal Failure Unit between 1978 and 2011 had their clinical records reviewed. SPSS 20 was utilised to perform Cox regression analysis and generate Kaplan Meier curves, with the aim of identifying factors associated with death and the continued need for HPN., Results: Case notes from 545 patients were reviewed. Overall survival (OS) in patients without malignancy at commencement of IF was 93%, 71%, 59% and 28% at 1, 5, 10 and 20 years after starting treatment. Crohn's disease, mesenteric ischaemia and chronic intestinal pseudo-obstruction were associated with a better OS than scleroderma and radiation enteritis on multivariate analysis. Older age at onset of IF was associated with poor OS, while shorter small bowel length or central line sepsis was not. 15% (25/170) of deaths were due to complications of HPN (central line sepsis = 10, IF-associated liver disease = 15). Continued HPN dependence in survivors was 83%, 63%, 59% and 53% at 1, 5, 10 and 15 years, respectively. Among the 153 patients without malignancy who achieved nutritional independence from HPN, 77 (50.3%) did so after surgical reconstruction of the alimentary tract (HPN duration mean 19 months, range 3-126 months). 76 patients (49.7%) weaned from HPN without undergoing surgical reconstruction., Conclusion: This is the largest reported data set on long-term survival and dependence on HPN and will inform the indications, benefits and risks of treatment in disease specific groups. A significant proportion of patients achieved nutritional autonomy without surgical intervention., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Catheter-related bloodstream infections (CRBSIs) are a serious complication in the provision of home parenteral nutrition (HPN). Antibiotic salvage of central venous catheters (CVCs) in CRBSI is recommended; however, this is based on limited reports. We assessed the efficacy of antibiotic salvage of CRBSIs in HPN patients., Materials and Methods: All confirmed CRBSIs occurring in patients receiving HPN in a national intestinal failure unit (IFU), between 1993 and 2011, were analyzed. A standardized protocol involving antibiotic and urokinase CVC locks and systemic antibiotics was used., Results: In total, 588 patients were identified with a total of 2134 HPN years, and 297 CRBSIs occurred in 137 patients (65 single and 72 multiple CRBSIs). The overall rate of CRBSI in all patients was 0.38 per 1000 catheter days. Most (87.9%) infections were attributable to a single microorganism. In total, 72.5% (180/248) of CRBSIs were salvaged when attempted (coagulase-negative staphylococcus, 79.8% [103/129], Staphylococcus aureus, 56.7% [17/30]; polymicrobial infections, 67.7% [21/30]; and miscellaneous, 66.1% [39/59]). CVC salvage was not attempted in 49 episodes because of life-threatening sepsis (n = 18), fungal infection (n = 7), catheter problems (n = 20), and CVC tunnel infection (n = 4). Overall, the CVC was removed in 33.7% (100/297) of cases. There were 5 deaths in patients admitted to the IFU for management of the CRBSI (2 severe sepsis at presentation, 3 metastatic infection)., Conclusions: This is the largest reported series of catheter salvage in CRBSIs and demonstrates successful catheter salvage in most cases when using a standardized protocol., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Persistent gastrocutaneous fistula (GCF) is a difficult to manage complication following gastrostomy tube removal, with leakage resulting in distressing sequelae including cutaneous injury, infection and dehydration. Many such patients are high-risk for invasive surgery and, to date, endoscopic closure techniques, including clipping systems, have limitations. We present the case of a 62-year-old woman with persistently leaking GCF 6 months postgastrostomy tube removal, despite maximal antisecretory therapy and postpyloric feeding, and describe failed attempted endoscopic closure with conventional clips. Treatment options were discussed and informed consent was given for an attempt at endoscopic closure using a novel radial closure device ('Padlock clip') combined with surgical de-epithelialisation, with the understanding that this device has never previously been used in this setting. At follow-up 2 weeks postprocedure, the patient was asymptomatic with complete healing of the GCF. This approach has advantages over other endoscopic closure techniques and can be considered as an alternative approach to GCF closure., (2015 BMJ Publishing Group Ltd.)

Problem: In 2010, there was a significant waiting list for admission to the intestinal failure unit (IFU) at the Salford Royal National Health Service (NHS) Foundation Trust. There had been a steady increase in the number of new patients referred to the IFU (89 patients 2005; 152 patients 2012) and the number of established patients requiring home parenteral nutrition (HPN) (135 patients 2005; 206 patients 2012) over the last decade. The impact of the resulting long waiting list for these complex patients was that patient deaths occurred in those awaiting admission., Design: Continuous improvement methodology using the model for improvement and sequential plan-do-study-act cycles., Setting: Salford Royal NHS Foundation Trust IFU; a large NHS teaching hospital in Northwest England., Key Measures for Improvement: The primary outcome measures were inpatient length of stay and time spent on waiting list prior to admission., Strategies for Change: A continuous improvement programme, supported by a project manager., Results: There has been a 21% reduction in average length of stay on the IFU from 55.7 to 44.0 days and a reduction of 72% in the average length of time new patients spent on the waiting list for admission from 65.7 to 18.5 days. These changes were associated with concomitant reduction in 30-day readmission rate from 12.1% to 4.5% and early suggestions of reduced inpatient and waiting list mortality., Conclusions: It is possible to improve the efficiency of a large national service for complex patients using quality improvement methodology, resulting in improved access and reduced waiting list mortality.

Precis: The aim of this study was to evaluate the safety and tolerance of a soybean/MCT/olive/fish oil emulsion in intestinal failure patients on long-term parenteral nutrition. 73 patients took part in a randomized, double-blind, multi-centre study. The study demonstrates that the lipid emulsion containing four different types of oils is safe and well tolerated in long-term PN., Background & Aim: Long-term safety and efficacy of a lipid emulsion containing soybean oil, medium-chain triglycerides (MCT), olive oil and fish oil and enriched in vitamin E have not yet been evaluated in adult patients requiring long-term parenteral nutrition (PN)., Methods: Randomised, controlled, double-blind, multicentre study in 73 patients with stable intestinal failure, requiring PN with either soybean/MCT/olive/fish emulsion (SMOFlipid, n = 34) or soybean emulsion (Intralipid, control n = 39) for 4 weeks. Safety and tolerance were monitored with standard clinical laboratory parameters, adverse events (AEs, according to the Common Terminology Criteria for Adverse Events (CTCAE) classification v 3.0) and vital signs. Fatty acid pattern in red blood cell phospholipids and plasma lipoproteins, serum Vitamin E, Interleukin (IL)-6, and soluble tumour necrosis (s-TNF)-receptor(R)II were also evaluated., Results: Mean concentrations of alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin, whilst remaining within the reference range, were significantly lower with soybean/MCT/olive/fish (SMOF) oil emulsion after the treatment period compared to control. Eicosapentaenoic acid, docosahexaenoic acid and n-3/n-6 fatty acid ratio increased in the SMOF group, while they remained unchanged in the control in plasma and RBC. Serum α-tocopherol concentrations significantly increased in the study group compared to control (p = 0.0004). IL-6 and sTNF-RII levels did not change during the study period. Grade 4 (serious) adverse events occurred in 2 SMOF patients and in 8 control patients (p = 0.03)., Conclusions: Soybean/MCT/olive/fish emulsion was safe and well tolerated over 4 weeks and leads to positive change in fatty acids profile., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Unlabelled: (18)F-FDG PET may assist decision making in ischemic cardiomyopathy. The PET and Recovery Following Revascularization (PARR 2) trial demonstrated a trend toward beneficial outcomes with PET-assisted management. The substudy of PARR 2 that we call Ottawa-FIVE, described here, was a post hoc analysis to determine the benefit of PET in a center with experience, ready access to (18)F-FDG, and integration with clinical teams., Methods: Included were patients with left ventricular dysfunction and suspected coronary artery disease being considered for revascularization. The patients had been randomized in PARR 2 to PET-assisted management (group 1) or standard care (group 2) and had been enrolled in Ottawa after August 1, 2002 (the date that on-site (18)F-FDG was initiated) (n = 111). The primary outcome was the composite endpoint of cardiac death, myocardial infarction, or cardiac rehospitalization within 1 y. Data were compared with the rest of PARR 2 (PET-assisted management [group 3] or standard care [group 4])., Results: In the Ottawa-FIVE subgroup of PARR 2, the cumulative proportion of patients experiencing the composite event was 19% (group 1), versus 41% (group 2). Multivariable Cox proportional hazards regression showed a benefit for the PET-assisted strategy (hazard ratio, 0.34; 95% confidence interval, 0.16-0.72; P = 0.005). Compared with other patients in PARR 2, Ottawa-FIVE patients had a lower ejection fraction (25% +/- 7% vs. 27% +/- 8%, P = 0.04), were more often female (24% vs. 13%, P = 0.006), tended to be older (64 +/- 10 y vs. 62 +/- 10 y, P = 0.07), and had less previous coronary artery bypass grafting (13% vs. 21%, P = 0.07). For patients in the rest of PARR 2, there was no significant difference in events between groups 3 and 4. The observed effect of (18)F-FDG PET-assisted management in the 4 groups in the context of adjusted survival curves demonstrated a significant interaction (P = 0.016). Comparisons of the 2 arms in Ottawa-FIVE to the 2 arms in the rest of PARR 2 demonstrated a trend toward significance (standard care, P = 0.145; PET-assisted management, P = 0.057)., Conclusion: In this post hoc group analysis, a significant reduction in cardiac events was observed in patients with (18)F-FDG PET-assisted management, compared with patients who received standard care. The results suggest that outcome may be benefited using (18)F-FDG PET in an experienced center with ready access to (18)F-FDG and integration with imaging, heart failure, and revascularization teams.

Objectives: We sought to determine the prognostic and incremental value of coronary artery disease (CAD) severity, coronary atherosclerosis, and left ventricular ejection fraction (LVEF) measured with cardiac computed tomography angiography (CTA)., Background: CTA is an emerging tool used for the detection of obstructive CAD. However, there are limited data supporting the prognostic value of 64-slice CTA and its ability to predict all-cause mortality and major adverse cardiac events such as cardiac death and nonfatal myocardial infarction., Methods: Consecutive patients (without history of revascularization, heart transplantation, and congenital heart disease) were prospectively enrolled. Each CTA was evaluated for CAD severity, total plaque score, and LVEF. Patients were followed, and all events were confirmed with death certificates or hospital or physician records and reviewed by a clinical events committee., Results: Between February 2006 and February 2008, 2,076 consecutive patients were prospectively enrolled and followed for a mean of 16 +/- 8 months. At follow-up, a total of 31 (1.5%) patients had cardiac death or nonfatal myocardial infarction and 47 (2.3%) had all-cause mortality or nonfatal myocardial infarction. Multivariate analysis showed that CAD severity (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.89 to 4.83) was a predictor of major adverse cardiac events and that LVEF (HR: 1.47; 95% CI: 1.17 to 1.86) had incremental value over CAD severity. Total plaque score had incremental value over CAD severity and LVEF for all-cause mortality and nonfatal myocardial infarction (HR: 1.17; 95% CI: 1.06 to 1.29)., Conclusions: Using CTA, CAD severity, LVEF, and total plaque score seems to have prognostic and incremental value over routine clinical predictors. Cardiac CTA seems to be a promising noninvasive modality with prognostic value., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Relative myocardial perfusion imaging may underestimate severity of coronary disease (CAD), particularly in cases of balanced ischemia. Can quantification of peak left (LV) and right (RV) ventricular Rb-82 uptake measurements identify patients with left main or 3 vessel disease?, Methods: Patients (N = 169) who underwent Rb-82 PET MPI and coronary angiography were categorized as having no significant coronary stenosis (n = 60), 1 or 2 vessel disease (n = 81), or left main disease/3 vessel disease (n = 28), based on angiography. Maximal LV and RV ventricular myocardial Rb-82 uptake was measured during stress and rest., Results: Failure to augment LV uptake by >or= 8500 Bq/cc at stress, predicted left main or 3 vessel disease with a sensitivity of 93% and specificity of 61% (area under curve = 0.83). A >or=10% increase in RV: LV uptake ratios with stress over rest was 93% specific (area under curve = 0.74) for left main or 3 vessel disease. These indices incrementally predicted left main or 3 vessel disease compared to models including age, gender, cardiac risk factors, and summed stress and difference scores., Conclusion: Quantifying maximal rest and stress LV and RV uptake with PET myocardial perfusion imaging may independently and incrementally identify patients with left main or 3 vessel disease.

Background: The PRKAG2 cardiac syndrome is an inherited metabolic disease of the heart characterized by excessive myocardial glycogen deposition. The biochemical alterations associated with this condition remain controversial and have not previously been studied in affected humans., Methods and Results: Positron emission tomography (PET) imaging was used to quantitatively assess myocardial glucose uptake (MGU) in 6 adult subjects with the PRKAG2 cardiac syndrome and 6 healthy, matched control subjects using the glucose analogue (18)F-Fluoro-2-deoxyglucose (FDG). Studies were performed under a euglycemic hyperinsulinemic clamp to ensure stable blood glucose levels. Rubidium-82 perfusion scans were performed to ensure that myocardial differences in myocardial glucose uptake were not the result of significant myocardial scar. In adult patients with phenotypic expression of disease, the median myocardial glucose uptake of the left ventricle was 0.18 mumol/min/g (interquartile range, 0.14, 0.24), compared with 0.40 mumol/min/g (interquartile range, 0.30 to 0.45) in the control group (P=0.01). The median blood glucose during FDG-PET imaging was 4.72 mmol/L (interquartile range, 4.32 to 4.97) in the PRKAG2 group and 4.38 mmol/L (interquartile range, 3.90, 4.79) in the control group (P=NS). The significant decrease observed in myocardial glucose uptake in affected patients occurred in the absence of significant myocardial scar., Conclusions: The PRKAG2 cardiac syndrome is associated with a reduction of glucose uptake in adult patients affected with this genetic condition. In this pilot study, (18)F-FDG-PET imaging is a useful tool to assess alterations in myocardial glucose transport in this inherited metabolic disease and provide insight into the biochemical pathophysiology of the diseased state.

Objectives: We sought to determine the incidence, clinical significance, and potential financial impact of noncardiac incidental findings (IF) identified with cardiac computed tomography (CT)., Background: Cardiac CT is gaining acceptance and may lead to the frequent discovery of extracardiac IF., Methods: Consecutive patients undergoing cardiac CT had noncardiac structures evaluated after full field of view (32 to 50 cm) reconstruction. IF were categorized as clinically significant (CS), indeterminate, or clinically insignificant. Patient follow-up was performed by telephone, and verified with hospital records and/or communication with physicians., Results: Of 966 patients (58 +/- 16 years of age, 55.4% men, >98% outpatients), 401 (41.5%) patients had noncardiac IF. A total of 12 (1.2%) patients had CS findings, and 68 (7.0%) patients had indeterminate findings. At follow-up (18.4 +/- 7.6 months), none of the indeterminate findings became CS. Although 3 patients with indeterminate findings were diagnosed with malignant lesions, they were unrelated to the IF. After adjusting for age, IF were not an independent predictor of noncardiac death. Noncardiac death and cancer death in patients with and without IF were not statistically different. One patient suffered a major complication related to the investigation of an IF. The total direct cost associated with investigating IF was Canadian $57,596 (U.S. $83,035)., Conclusions: Although noncardiac IF are common, clinically significant or indeterminate IF are less prevalent. Rates of death were similar in patients with and without IF, and IF was not an independent predictor of noncardiac death. The investigation of IF is not without cost or risk. Larger studies are required to assess the potential mortality benefit of identifying IF.

Background: Computed tomographic coronary angiography (CTA), given its high negative predictive value, is a potential gatekeeper for invasive coronary angiography (ICA). Before CTA can be further accepted into clinical practice, its impact on healthcare resources needs to be better understood. We sought to determine the clinical impact of CTA on ICA referrals, CTA accuracy, and normalcy rate., Methods and Results: To determine the impact of CTA, consecutive patients (n=7017) undergoing ICA before and after implementing a dedicated cardiac CT program were reviewed and compared with 3 other centers (n=11 508). To determine CTA accuracy, we evaluated consecutive CTA patients who underwent ICA. For normalcy rate, we identified patients with a low pretest probability for obstructive coronary artery disease. With the implementation of a cardiac CT program, the frequency of normal ICA decreased from 31.5% (1114 of 3538 patients) to 26.8% (932 of 3479 patients) (P<0.001). These findings were significantly different (P=0.003) from the 3 centers, in which normal ICAs were unchanged (30.0% [1870 of 6224 patients] to 31.0% [1642 of 5284 patients]). CTA had excellent per-patient sensitivity (99% [CI, 95% to 100%]), positive predictive value (92% [CI, 86% to 96%]) and negative predictive value (95% [CI, 72% to 100%]). Because of referral bias, specificity (64% [CI, 44% to 81%]) was low; however, the normalcy rate of CTA was 94% (CI, 90% to 97%). After adjusting for referral bias, the adjusted sensitivity was 90% (CI, 89% to 91%), and the adjusted specificity was 95% (CI, 94% to 96%), with positive and negative predictive values of 92% (CI, 91% to 93%) and 93% (CI, 92% to 94%), respectively., Conclusions: The clinical implementation of CTA appears to positively impact ICA by reducing the frequency of normal ICA. The operating characteristics of CTA support its potential role as a tool useful in ruling out obstructive coronary artery disease.

Background: The feasibility and value of transthoracic dobutamine stress echocardiography (DSE) in patients scheduled for bariatric surgery has not been investigated., Methods: We evaluated 611 patients (86.6% female, 42 +/- 10 years, 136 +/- 18 kg, BMI 48.0 +/- 6.1 kg/m2) referred for DSE prior to surgery between February 2000 and July 2005. Mortality and major cardiovascular events (cardiac death, acute coronary syndrome, and urgent revascularization) were recorded 30-days postoperatively and at 6 months., Results: Adequate baseline imaging quality was achieved in 590 patients (96.6%), with use of echocardiographic contrast agents in 426 patients (72.2%); the remaining 21 patients (3.4%) were referred for alternative preoperative testing. There were no serious adverse events during DSE, which was negative in 545 patients (92.4%). The test was inconclusive in 38 patients (6.4%), requiring alternative investigations, and positive in 7 patients (1.2%). Eventually, 595 patients proceeded to surgery: 539 with DSE-based risk stratification and 56 with risk stratification based on alternative testing. Laparoscopic procedures were employed in 77.0% of patients. There were 3 perioperative deaths, all attributed to sepsis (perioperative mortality 0.50%), but no major cardiovascular events at 30-days. One patient (evaluated prior to surgery with alternative testing) experienced an acute coronary syndrome during the following 6 months (event rate 0.17%)., Conclusion: Transthoracic DSE is feasible and safe in morbidly obese patients undergoing bariatric surgery; implementation of echocardiographic contrast agents allows for adequate imaging quality in the majority of these patients. However, the very low risk of contemporary bariatric procedures questions the need for routine preoperative stress testing in asymptomatic patients.

A 37-year-old man presented with severe dilated cardiomyopathy secondary to occult aortic coarctation. He was successfully managed with combined orthotopic heart transplantation and aortic coarctation repair.

Background: Internationally, differences have been noted in how specialist cardiologists and general physicians manage acute coronary syndromes (ACS). Whether a similar practice difference exists in New Zealand is unclear., Aim: To test the hypothesis that management differences exist between cardiologists and general physicians in patients presenting with a non-ST-segment elevation acute coronary syndrome in a New Zealand setting-and whether these differences (if present) impact on patient outcome., Methods: A retrospective chart review of 324 consecutive patients presenting with a non-ST-segment elevation acute coronary syndrome to Taranaki Base and Waikato Hospitals from 1 January 1999 was undertaken. Patients in Taranaki were managed by general physicians and in Waikato they were managed by cardiologists., Results: Patients presenting to Taranaki Base Hospital were more likely to have high-risk ECG changes with ST-segment depression noted in 34.4% of patients there compared to 16.8% of patients in Waikato (p<0.001). Medical management during patient stabilisation was similar in Taranaki and Waikato with high use of anti-thrombotic (89%) and anti-platelet therapy (94%), respectively. However angiography (5.1% versus 23.4%; p=0.0045) and revascularisation procedures (4% versus 16.7%; p=0.0002) were performed less frequently in Taranaki. No significant difference was noted in mortality at 6 months (9.6% in Waikato versus 13.4% in Taranaki; p=0.4) Readmission rates were also similar; occurring overall in approximately one-quarter of the study population., Conclusion: In New Zealand, differences exist in how cardiologists and general physicians manage non-ST-elevation acute coronary syndrome. In particular, the low referral rates for angiography by general physicians is of concern and requires correction as current best-practice guidelines suggest high-risk patients are disadvantaged by a conservative approach to management.