Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.

AIMS: Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70-0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81-0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120-150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18-0.74) and 0.21 (95% CI: 0.072-0.61), respectively. CONCLUSION: Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

Respiratory gated and prolonged acquisition 18F-FDG PET improve preoperative assessment of colorectal liver metastases.

BACKGROUND: Detection of small liver metastases from colorectal cancer by 18F-FDG PET/CT is hampered by high physiologic uptake in the liver parenchyma and respiratory movements during image acquisition. PURPOSE: To investigate whether two tailored 18F-FDG PET liver acquisitions (prolonged liver acquisition time [PL-PET] and repeated breath-hold respiratory gated liver acquisition [RGL-PET]) would improve detection of colorectal liver metastases, when added to a standard whole body PET (WB-PET). MATERIAL AND METHODS: Twenty consecutive patients referred to our hospital for surgical treatment of colorectal liver metastases diagnosed with contrast-enhanced CT underwent preoperative 18F-FDG PET/CT tailored for detection of liver metastases. Concordance between preoperative imaging results and true findings (histology and/or follow-up imaging) as well as changes in clinical management, based on 18F-FDG PET/CT findings, were documented. Background noise, defined as the standard deviation measured in a reference region within the normal liver parenchyma, was compared between the three 18F-FDG PET/CT protocols. RESULTS: WB-PET, PL-PET, and RGL-PET showed suspicious liver lesions in 18 out of 20 patients. Compared to WB-PET alone, the combination of PL-PET and RGL-PET showed additional lesions in the liver in seven out of the 18 patients. The combination of all three PET acquisitions changed clinical management in four patients. Two patients with negative PET results were later found to have benign liver lesions. CONCLUSION: The addition of tailored liver-specific 18F-FDG PET/CT protocols (PL-PET and RGL-PET) to a WB-PET, improved the detection of intrahepatic colorectal metastases, compared to WB-PET alone. Such add-ons can change clinical patient management of potentially resectable colorectal liver metastases.

A novel clinical method for quantification of regional left ventricular pressure-strain loop area: a non-invasive index of myocardial work.

AIMS: Left ventricular (LV) pressure-strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non-invasive method to measure LV pressure-strain loop area. METHODS AND RESULTS: Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs (n = 12) and non-invasively in patients (n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation (r = 0.96) and a good agreement between estimated LV pressure-strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation (r = 0.99) and a good agreement between pressure-strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure-strain loop area reflected work when incorporating changes in local LV geometry (r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET (r = 0.81). CONCLUSIONS: The novel non-invasive method for regional LV pressure-strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia.

Scar imaging in the dyssynchronous left ventricle: Accuracy of myocardial metabolism by positron emission tomography and function by echocardiographic strain.

PURPOSE: Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. METHODS: In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. RESULTS: Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90-1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71-0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80). CONCLUSIONS: In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar. CLINICAL TRIAL REGISTRATION: The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185).

Regional myocardial work by cardiac magnetic resonance and non-invasive left ventricular pressure: a feasibility study in left bundle branch block.

AIMS: Regional myocardial work may be assessed by pressure-strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP. METHODS AND RESULTS: Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure-strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively). CONCLUSION: FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.

Carotid plaque inflammation assessed with (18)F-FDG PET/CT is higher in symptomatic compared with asymptomatic patients.

BACKGROUND: Carotid artery plaque inflammation is thought to be an important marker of plaque vulnerability and increased stroke risk. AIM: The main aim of this study was to assess the level of agreement between 2-deoxy-2-[(18)F] fluoro-D-glucose (18F-FDG) uptake on PET (positron emission tomography) scan in carotid plaques, with cerebrovascular symptoms, carotid plaque ultrasound echogenicity and histological assessments of plaque inflammation. METHODS: Thirty-six patients with ≥70% carotid stenosis scheduled for carotid endarterectomy underwent a Colour Duplex ultrasound, (18)F-FDG PET/CT and blood tests less than 24 h prior to surgery. Plaques were defined as symptomatic when associated with ipsilateral cerebral ischemic symptoms within 30 days prior to inclusion. Plaques were assessed histologically following endarterectomy. The level of agreement between (18)F-FDG uptake (mean SUVmax and SUVmax ), and target-to-background ratio, symptoms, plaque echolucency, and histological evidence of inflammation was assessed. RESULTS: The amount of (18)F-FDG uptake in plaques and the amount of inflammation on histological assessment were significantly correlated (r = 0·521, P = 0·003). (18)F-FDG uptake was significantly higher in symptomatic plaques with median SUVmax 1·75 (1·26-2·04) in symptomatic, and 1·43 (1·15-2·28) in asymptomatic patients (P = 0·03). (18)F-FDG uptake was also positively correlated with echolucency on Doppler ultrasound (P = 0·03). CONCLUSION: (18)F-FDG uptake on PET/CT correlated with histological assessments of inflammation and was higher in patients with symptomatic compared with asymptomatic carotid artery plaques. These results support the use of (18)F-FDG PET/CT in the detection inflammation in carotid atherosclerosis, which may be of help in the detection of vulnerable plaques.

Temporal relation between leukocyte accumulation in muscles and halted recovery 10-20 h after strength exercise.

Effects of normal strength exercise on leukocyte accumulation were examined in 10 well-trained male subjects (27.2 +/- 2.7 yr). The workout, consisting of five maximal sets of three repetitions of leg press exercise and five maximal sets of six repetitions of knee extension exercise, was performed with the dominant leg, and the other leg served as control. Repeated maximal isokinetic knee extensions at 60 degrees /s were performed to evaluate neuromuscular fatigue and recovery after the workout. Accumulation of leukocytes was assessed with 99mTc-labeled cells, and repeated images of the thighs were taken 1-24 h after the workout. Maximal force-generating capacity in the exercised leg was reduced by 17 +/- 2% (P < 0.01) after the workout. The course of recovery followed a biphasic pattern characterized by halted recovery 10-23 h after exercise. The presence of leukocytes was approximately 10% higher in the exercised than in the control thigh 10 h after exercise (P < 0.05). This difference increased to approximately 15% at 20 h after exercise (P < 0.05). The retarded recovery of maximal force-generating capacity 10-20 h after exercise, together with a significant infiltration of leukocytes in exercised muscle during the same time interval, shows a temporal relation between leukocyte infiltration and impaired recovery.

Gastric emptying in children with gastroesophageal reflux and in healthy children.

PURPOSE: The aim of this report is to examine whether children with gastroesophageal reflux (GER) have delayed gastric emptying compared to healthy children. METHODS: All patients had GER verified by 24-hour pH monitoring. Gastric emptying of cow's milk was examined by radionuclide scintigraphy in 51 patients with GER and in 24 controls. Gastric emptying rate was expressed as exponential half time (T1/2). RESULTS: Median age was 4.4 years [range 0.1-15.4] in patients and 6.1 years [range 2.5-10.0] in controls (p=.10). A wide range of gastric emptying rates was observed both in GER patients [range 16-121] and controls [range 29-94]. One GER patient (2%) had slower gastric emptying (T1/2=121 min) than the healthy child with the longest T1/2 (94 min). Mean T1/2 was 49 minutes (SD 20.1) and 46 minutes (SD 14.2) in GER patients and controls, respectively (p=.51). CONCLUSIONS: Gastric emptying rate of milk was not significantly different between children with GER and healthy children. A wide range of gastric emptying rates was observed in both groups.

Time course of leukocyte accumulation in human muscle after eccentric exercise.

PURPOSE: To investigate the time course of leukocyte accumulation in eccentric exercised human muscles and its relation to recovery of muscle function and soreness. METHODS: Eleven young males performed 300 unilateral, maximal voluntary, eccentric actions with the musculus quadriceps femoris (30 degrees x s(-1)). Before and at regular intervals for 7 d after exercise, force-generating capacity was measured with maximal concentric knee extensions (60 degrees x s(-1)). Accumulation of radiolabeled (autologous) leukocytes was measured with scintigraphy. Biopsies from musculus vastus lateralis were obtained 0.5, 4, 8, 24, 96, and 168 h after exercise from both the exercised leg and the control leg. Muscle cross-sections were stained with antibodies against leukocytes (CD16 and CD68). Muscle soreness was rated on a visual analog scale. RESULTS: Immediately after exercise, the subjects' ability to generate force was reduced by 47 +/- 5%. Muscle function recovered slowly and was not fully restored after 1 wk. Radiolabeled leukocytes accumulated in the muscles during the first hour (3-24 h) after exercise, and leukocytes were at the same time observed histologically, primarily in the endomysium and perimysium. A part of the accumulated radiolabeled leukocytes appeared to be located within local blood vessels. The highest numbers of CD16(+) and CD68(+) cells were found 4 and 7 d after exercise. There was a positive correlation between accumulation of radiolabeled leukocytes and muscle weakness measured 1-3 d after exercise (r = 0.8, P < 0.05) and, surprisingly, a negative correlation between radiolabeled leukocyte accumulation and muscle soreness (r = -0.96, P < 0.01). CONCLUSION: Exercise-induced muscle damage initiated a rapid local inflammatory response that gradually increased over the next days. Halted recovery of muscle function was associated with local accumulation of leukocytes, whereas muscle soreness could not be explained by the presence of leukocytes.

123 I-mIBG scintigraphy to predict inducibility of ventricular arrhythmias on cardiac electrophysiology testing: a prospective multicenter pilot study.

BACKGROUND: Disturbances of autonomic function after infarction are associated with both total mortality and sudden death. Although many imaging techniques for assessing the cardiac autonomic nervous system have been studied, the clinical usefulness of these techniques remains uncertain. This exploratory pilot study examined the relationship between abnormalities of ventricular sympathetic innervation delineated by scintigraphic imaging with (123)I-mIBG and inducible ventricular tachyarrhythmias in patients with left ventricular dysfunction and previous myocardial infarction. METHODS AND RESULTS: Fifty patients underwent electrophysiological (EP) testing and 15-minute and 4-hour planar and single photon emission computed tomography (SPECT) imaging with (123)I-mIBG and SPECT imaging with (99m)Tc-tetrofosmin. The primary efficacy variables were the 4-hour heart:mediastinum ratio (H/M) and the (123)I-mIBG/(99m)Tc-tetrofosmin SPECT mismatch score. EP studies were categorized as positive (EP(+)) or negative (EP(-)) for inducibility of sustained (>30 seconds) ventricular tachyarrhythmias. Thirty patients were EP(+), and 20 were EP(-). There were no significant differences in the 4-hour H/M ratios or (123)I-mIBG/(99m)Tc-tetrofosmin SPECT mismatch scores between the two groups. In a multivariable analysis using all (123)I-mIBG and (99m)Tc-tetrofosmin SPECT measurements, the only variable that showed a significant difference between EP(+) and EP(-) patients was the 4-hour (123)I-mIBG SPECT defect score. A 4-hour (123)I-mIBG SPECT defect score of > or =37 yielded a sensitivity of 77% and specificity of 75% for predicting EP results. CONCLUSIONS: The standard indices of (123)I-mIBG imaging (H/M and innervation-perfusion mismatch score) are not predictive of EP test results. The association of (123)I-mIBG SPECT defect severity with EP test inducibility in this exploratory study will require confirmation in a larger cohort of patients.