Quantitative blood flow evaluation of vasodilation-stress compared with dobutamine-stress in patients with end-stage liver disease using 82Rb PET/CT.

BACKGROUND: Our aim was to determine if end-stage liver disease (ESLD) is associated with an attenuated response to vasodilator-stress or dobutamine-stress using 82Rb-PET MPI with blood flow quantification. METHODS AND RESULTS: Pre-liver transplant patients who had a normal dipyridamole-stress (n = 27) or dobutamine-stress (n = 26) 82Rb PET/CT MPI study with no identifiable coronary artery calcium were identified retrospectively and compared to a prospectively identified low-risk of liver disease dipyridamole-stress control group (n = 20). The dipyridamole-stress liver disease group had a lower myocardial flow reserve (MFR) (1.89 ± 0.79) than the control group (2.79 ± 0.96, P < .05). The dobutamine-stress group had a higher MFR than both other groups (3.69 ± 1.49, P < .05). A moderate negative correlation between MELD score and MFR was demonstrated for the dipyridamole-stress liver disease group (r = - 0.473, P < .05). This correlation was not observed for the dobutamine-stress liver disease group (r = - 0.253, P = .21). The liver failure group as a whole (n = 53) had a higher resting myocardial blood flow (0.97 ± 0.33 mL/min/g) than the control group (0.82 ± 0.26, P < .05). CONCLUSION: Dipyridamole demonstrates an attenuated vasodilatory response in ESLD patients compared to a non-ESLD control group related to higher resting blood flow and comparatively reduced stress blood flow. Dobutamine does not demonstrate this effect implying it may be the preferred pharmacologic MPI stress agent for ESLD patients.

Cardiac EASE (Ensuring Access and Speedy Evaluation)--design of a single point of entry and a multidisciplinary team to reduce waiting times in the Canadian health care system.

Out-patient cardiac consultation in academic group practices often lacks a coordinated intake process, making it difficult to perform prospective testing or to direct undifferentiated consultations to the cardiologist with the shortest waiting list. We created a programmatic approach, with a single point of entry to improve the efficiency of cardiology consultation, without departing from the Canada Health Act. The purpose of this paper is to describe the design of Cardiac EASE.

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. METHODS: 82Rb or 13N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. RESULTS: Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. CONCLUSION: Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit.

Successful recycling of a previously transplanted heart: another option for limited resources.

We report a case of successful reuse of a previously transplanted heart. The organ was retransplanted 16 days after the initial transplantation into a 60-year-old man who had previously received a left ventricular assist device.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

Cardiac positron emission tomography: current clinical practice.

In the last two decades, the field of nuclear cardiology has experienced significant progress. The introduction of positron emission tomography (PET) imaging represented a major breakthrough that has significantly contributed to a better understanding of physiology and pathophysiology of several heart diseases. Currently, PET imaging is recognized as a well-established method to assess cardiac perfusion, function, metabolism, and viability. This article summarizes the main clinical applications of state-of-the art cardiac PET technology.

Cardiac EASE (Ensuring Access and Speedy Evaluation) - the impact of a single-point-of-entry multidisciplinary outpatient cardiology consultation program on wait times in Canada.

BACKGROUND: Universal access to health care is valued in Canada but increasing wait times for services (eg, cardiology consultation) raise safety questions. Observations suggest that deficiencies in the process of care contribute to wait times. Consequently, an outpatient clinic was designed for Ensuring Access and Speedy Evaluation (Cardiac EASE) in a university group practice, providing cardiac consultative services for northern Alberta. Cardiac EASE has two components: a single-point-ofentry intake service (prospective testing using physician-approved algorithms and previsit triage) and a multidisciplinary clinic (staffed by cardiologists, nurse practitioners and doctoral-trained pharmacists). OBJECTIVES: It was hypothesized that Cardiac EASE would reduce the time to initial consultation and a definitive diagnosis, and also increase the referral capacity. METHODS: The primary and secondary outcomes were time from referral to initial consultation, and time to achieve a definitive diagnosis and management plan, respectively. A conventionally managed historical control group (three-month pre-EASE period in 2003) was compared with the EASE group (2004 to 2006). The conventional referral mechanism continued concurrently with EASE. RESULTS: A comparison between pre-EASE (n=311) and EASE (n=3096) revealed no difference in the mean (+/- SD) age (60+/-16 years), sex (55% and 52% men, respectively) or reason for referral, including chest pain (31% and 40%, respectively) and arrhythmia (27% and 29%, respectively). Cardiac EASE reduced the time to initial cardiac consultation (from 71+/-45 days to 33+/-19 days) and time to a definitive diagnosis (from 120+/-86 days to 51+/-58 days) (P<0.0001). The annual number of new referrals increased from 1512 in 2002 to 2574 in 2006 due to growth in the Cardiac EASE clinic. The number of patients seen through the conventional referral mechanism and their wait times remained constant during the study period. CONCLUSIONS: Cardiac EASE reduced wait times, increased capacity and shortened time to achieve a diagnosis. The EASE model could shorten wait times for consultative services in Canada.

Supratherapeutic response to ezetimibe administered with cyclosporine.

OBJECTIVE: To report the case of a patient who underwent orthotopic heart transplant (OHT) and demonstrated a supratherapeutic response to ezetimibe when administered with cyclosporine. CASE SUMMARY: Ezetimibe 10 mg/day was added to the lipid-lowering regimen (atorvastatin 40 mg/day) of a 64-year-old male patient after OHT to achieve a target low-density lipoprotein cholesterol (LDL-C) level < or = 97 mg/dL, as recommended by national guidelines. After 2 months of ezetimibe, the patient's LDL-C level had decreased by 60% to 51 mg/dL. Subsequently, the dose of ezetimibe was reduced to 5 mg/day and, after another 2 months, a repeat lipid panel revealed LDL-C 57 mg/dL. DISCUSSION: Hyperlipidemia is a common problem among heart transplant recipients. Combination therapy using a statin plus ezetimibe appears to be an attractive option to achieve target lipid levels in this population. However, the manufacturer warns that ezetimibe should be administered cautiously in patients concomitantly receiving cyclosporine. Unpublished data suggest a pharmacokinetic interaction between ezetimibe and cyclosporine that results in a significant 2.3- to 12-fold increase in exposure to total ezetimibe. An objective causality assessment in this case revealed that this supratherapeutic LDL-C reduction was probably related to coadministration of ezetimibe and cyclosporine. A potential mechanism to explain this interaction might be an alteration in glucuronidation induced by cyclosporine. CONCLUSIONS: When ezetimibe is prescribed for patients concomitantly receiving cyclosporine, it should be initiated at a lower than recommended dose (> or = 5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.