Treatment with enalapril and not diltiazem ameliorated progression of chronic kidney disease in rats, and normalized renal AT1 receptor expression as measured with PET imaging.

ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8-10 weeks. Kidney AT1R expression was assessed using in vivo [18F]fluoropyridine-losartan PET and in vitro autoradiography. Compared to shams, Nx rats exhibited higher systolic blood pressure that was reduced by both enalapril and diltiazem. At 18-20 weeks, plasma creatinine and albuminuria were significantly increased in Nx, reduced to sham levels in NxE, but enhanced in NxD rats. Enalapril treatment decreased kidney angiotensin II whereas diltiazem induced significant elevations in plasma and kidney levels. Reduced PET renal AT1R levels in Nx were normalized by enalapril but not diltiazem, and results were supported by autoradiography. Reduction of renal blood flow in Nx was restored by enalapril, while no difference was observed in myocardial blood flow amongst groups. Enhanced left ventricle mass in Nx was not reversed by enalapril but was augmented with diltiazem. Stroke volume was diminished in untreated Nx compared to shams and restored with both therapies. [18F]Fluoropyridine-Losartan PET allowed in vivo quantification of kidney AT1R changes associated with progression of CKD and with various pharmacotherapies.

Routine versus selective cardiac magnetic resonance in non-ischemic heart failure - OUTSMART-HF: study protocol for a randomized controlled trial (IMAGE-HF (heart failure) project 1-B).

BACKGROUND: Imaging has become a routine part of heart failure (HF) investigation. Echocardiography is a first-line test in HF given its availability and it provides valuable diagnostic and prognostic information. Cardiac magnetic resonance (CMR) is an emerging clinical tool in the management of patients with non-ischemic heart failure. Current ACC/AHA/CCS/ESC guidelines advocate its role in the detection of a variety of cardiomyopathies but there is a paucity of high quality evidence to support these recommendations.The primary objective of this study is to compare the diagnostic yield of routine cardiac magnetic resonance versus standard care (that is, echocardiography with only selective use of CMR) in patients with non-ischemic heart failure. The primary hypothesisis that the routine use of CMR will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and HF with preserved ejection fraction. DESIGN: Tertiary care sites in Canada and Finland, with dedicated HF and CMR programs, will randomize consecutive patients with new or deteriorating HF to routine CMR or selective CMR. All patients will undergo a standard clinical echocardiogram and the interpreter will assign the most likely HF etiology. Those undergoing CMR will also have a standard examination and will be assigned a HF etiology based upon the findings. The treating physician's impression about non-ischemic HF etiology will be collected following all baseline testing (including echo ± CMR). Patients will be followed annually for 4 years to ascertain clinical outcomes, quality of life and cost. The expected outcome is that the routine CMR arm will have a significantly higher rate of infiltrative, inflammatory, hypertrophic, ischemic and 'other' cardiomyopathy than the selective CMR group. DISCUSSION: This study will be the first multicenter randomized, controlled trial evaluating the role of CMR in non-ischemic HF. Non-ischemic HF patients will be randomized to routine CMR in order to determine whether there are any gains over management strategies employing selective CMR utilization. The insight gained from this study should improve appropriate CMR use in HF. TRIAL REGISTRATION: NCT01281384.

Single-phase CT aligned to gated PET for respiratory motion correction in cardiac PET/CT.

UNLABELLED: Respiratory motion can induce artifacts in cardiac PET/CT because of the misregistration of the CT attenuation map and emission data. Some solutions to the respiratory motion problem use 4-dimensional CT, but this increases patient radiation exposure. Realignment of 3-dimensional CT and PET images can remove apparent uptake defects caused by mispositioning of the PET emission data into the lung regions on the CT scan. This realignment is typically done as part of regular clinical quality assurance. We evaluated a method to improve on this standard approach, without increasing the radiation exposure to the patient, by acquiring a respiration-gated PET scan and separately aligning the 3-dimensional CT scan to each phase of the PET study. METHODS: Three hundred ten clinical PET perfusion scans ((82)Rb [n = 187] and (13)N-ammonia [n = 123]) were retrospectively assessed. Studies were respiration-gated, and motion was measured between inspiration and expiration phases. Those studies with motion > or = 8 mm were evaluated for significant differences between inspiration and expiration. Studies with significant differences were reprocessed with the phase-alignment approach. The observed motion with (82)Rb and (13)N-ammonia for rest and stress imaging was also compared. RESULTS: Twenty-three scans (7.41%) had motion > or = 8 mm, and 9 of these had significant differences between inspiration and expiration, suggesting the presence of respiratory artifacts. Phase-aligned respiratory motion compensation reduced this difference in 8 of 9 cases (89%). No significant differences were observed between (82)Rb and (13)N-ammonia, and motion during stress imaging was correlated with motion at rest (r = 0.61, P < 0.001). CONCLUSION: Phase-aligned correction improves the consistency of PET/CT perfusion images by reducing discrepancies caused by respiratory motion. This new approach to CT-based attenuation correction has no additional patient radiation exposure and may improve the specificity of PET perfusion imaging.

Effect of lateral wall scar on reverse remodeling with cardiac resynchronization therapy.

BACKGROUND: Up to 50% of patients do not respond to cardiac resynchronization therapy (CRT). Recent work has focused on quantifying left ventricular (LV) scar, with conflicting results. Some studies have shown that the global extent of LV scar is important, whereas others found the size of the septal or lateral wall scar to be key. OBJECTIVE: This study sought to examine the relative importance of the size and distribution of LV scar in determining reverse remodeling to CRT. METHODS: Forty-nine patients had pre-implantation rubidium-82 and fluorine-18-fluorodeoxyglucose positron emission tomography scanning. Total and regional LV scar size were calculated. Response to CRT was pre-specified as > or =10% improvement in LV end-systolic volume and/or > or =5% absolute ejection fraction improvement. RESULTS: Responders (n = 31) had significantly less lateral wall scar than responders (5.6% compared with 24.5%, P = .008) but a similar extent of global and septal scar. In the ischemic group, responders' median lateral wall scar size was 11.2% (IQR 0.0 to 31.2), compared with 47.8% (IQR 21.2 to 73.4) P = .052. In the ischemic group, for each 5% absolute decrease in lateral scar size, the odds ratio of being a responder was 1.87 (95% CI: 1.11 to 3.15, P = .018). In the nonischemic group, median lateral wall scar size of responders was 3.4% (IQR 0.0 to 10.3) compared with the nonresponders, 14.4% (IQR 9.0 to 27.8), P = .046. CONCLUSION: Responders had significantly less lateral wall scar than nonresponders, but a similar extent of global and septal scar. This held true in both ischemic and nonischemic cardiomyopathy patients.