Abstract Objectives This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver ...transplantation (LT). Background mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it. Methods In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability,123 -meta-iodobenzylguanidine heart/mediastinum (123 -MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA). Results Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score,123 -MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The123 -MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either123- MIBG H/M ratio ( S MIBG ) or HRRA ( S atropine ). AUC of S MIBG and S atropine were greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of S MIBG , S atropine , and a reference clinical model (AUC: 0.785) were similar. Conclusions Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that evaluate cardiac dysautonomia,123 -MIBG scintigraphy and heart rate response to atropine had better prognostic accuracy. Multivariate models did not improve significantly prediction of outcome.
By removing the main source of the mutated TTR, liver transplantation (LT) has become the standard treatment for ATTR (1). Because the demand for liver grafts exceeds the number of available organs ...and because new treatments have recently emerged, screening patients at high risk of death after LT is critical (2). The risk score was built from variables that measured the cardiac and neurological status regardless of mutation type. ...our proposed score should be useful to gauge the risk of patients with rare variants of TTR and to take into account the phenotypic variability encountered among patients with a similar mutation.
Familial amyloid polyneuropathy (FAP) is an autosomic dominant disease with a high rate of conduction disorders and increased risk of sudden death. Prophylactic cardiac pacing may be considered in ...asymptomatic patients with FAP. However, the potential benefits are unknown.
To document conduction disorders in a large series of FAP and the incidence of high-degree atrioventricular (AV) block in patients with prophylactic pacemaker (PM).
From January 1999 to January 2010, 262 patients with FAP were retrospectively evaluated. Prophylactic PM was implanted in patients with His-ventricular interval ≥ 70 ms, His-ventricular interval >55 ms associated with a fascicular block, a first-degree AV block, or a Wenckebach anterograde point ≤ 100 beats/min. The spontaneous AV conduction was then analyzed by temporarily inhibiting the PM.
As compared with patients with prophylactic PM (n = 100) and patients implanted given a class I/IIa indication (n = 18), the patients who did not require PM (n = 144) were younger and displayed less severe cardiac involvement. Follow-up after prophylactic PM implantation was analyzed in 95 of the 100 patients over 45 ± 35 months, and a high-degree AV block was documented in 24 of the 95 patients (25%). The risk of high-degree AV block was higher in patients with first-degree AV block or Wenckebach anterograde point ≤ 100 beats/min (hazard ratio 3.5; 95% confidence interval 1.2-10) while microvoltage on surface electrocardiogram reduced the risk (hazard ratio 0.2; 95% confidence interval 0.1-0.7).
In FAP with conduction disorders, prophylactic PM implantation prevented major cardiac events in 25% of the patients over a 45-month mean follow-up. It is suggested that prophylactic PM implantation prevented symptomatic bradycardia in these patients.
Objective Abdominal aortic aneurysm (AAA) is a frequent form of atherothrombotic disease, whose natural history is to enlarge and rupture. Indicators other than AAA diameter would be useful for ...preventive surgery decision-making, including positron-emission tomography (PET) methods permitting visualization of aortic wall leukocyte activation relevant to prognostic AAA evaluation. In this study, we compare three PET tracers of activated leukocytes, 18F-fluoro-deoxy-glucose (FDG), 18F-fluoro-methyl-choline (FCH), and 18F-DPA714 (a peripheral benzodiazepine receptor antagonist) for in vivo PET quantification of aortic wall inflammation in rat experimental AAAs, in correlation with histopathological studies of lesions. Methods AAAs were induced by orthotopic implantation of decellularized guinea pig abdominal aorta in 46 Lewis rats. FDG-PET (n = 20), FCH-PET (n = 8), or both (n = 12) were performed 2 weeks to 4 months after the graft, 1 hour after tracer injection (30 MBq). Six rats (one of which had FDG-PET) underwent 18F-DPA714-PET. Rats were sacrificed after imaging; AAAs and normal thoracic aortas were cut into axial sections for quantitative autoradiography and histologic studies, including ED1 (macrophages) and CD8 T lymphocyte immunostaining. Ex vivo staining of AAAs and thoracic aortas with 18F-DPA714 and unlabeled competitors was performed. Results AAAs developed in 35 out of 46 cases. FCH uptake in AAAs was lower than that of FDG in all cases on imaging, with lower AAA-to-background maximal standardized uptake value (SUVmax ) ratios (1.78 ± 0.40 vs 2.71 ± 0.54; P < .01 for SUVmax ratios), and lower AAA-to-normal aorta activity ratios on autoradiography (3.52 ± 1.26 vs 8.55 ± 4.23; P < .005). FDG AAA-to-background SUVmax ratios correlated with the intensity of CD8 + ED1 staining ( r = .76; P < .03). FCH AAA-to-background SUVmax ratios correlated with the intensity of ED1 staining ( r = .80; P < .03). 18F-DPA714 uptake was similar in AAAs and in normal aortas, both in vivo and ex vivo. Conclusions In rat experimental AAA, characterized by an important aortic wall leukocytes activity, FDG-PET showed higher sensitivity than FCH-PET and 18F-DPA714-PET to detect activated leukocytes. This enhances potential interest of this tracer for prognostic evaluation of AAA in patients.
Abstract Cardiovascular magnetic resonance (CMR) has evolved from a pioneering research tool to an established noninvasive imaging method for detecting inducible myocardial perfusion deficits. In ...this consensus document, experts of different imaging techniques summarize the existing body of evidence regarding CMR perfusion as a viable complement to other established noninvasive tools for the assessment of perfusion and discuss the advantages and pitfalls of the technique. A rapid, standardized CMR perfusion protocol is described, which is safe, clinically feasible, and cost-effective for centers with contemporary magnetic resonance equipment. CMR perfusion can be recommended as a routine diagnostic tool to identify inducible myocardial ischemia.
A growing body of evidence suggests that the arrhythmogenic substrate underlying Brugada syndrome (BrS) is located in the right ventricular outflow tract (RVOT), and electrophysiological ...abnormalities recently evidenced most commonly concur in conduction slowing. Also, imaging studies reported wall motion abnormalities of the RVOT in patients with BrS, with a various extent of RV remodeling. However, there are no data regarding a potential relationship between electrophysiological alterations and contraction abnormalities in BrS.
We aimed to assess (1) the potential relationship between contraction delays of the RV quantified by phase analysis of equilibrium radionuclide angiography (ERNA), and the spontaneous ST-segment elevation pattern; and (2) to evidence RV remodeling in patients with BrS.
Seventy patients with BrS and 18 control subjects were included in the study. For the purpose of the study, the spontaneous ST-segment elevation pattern was graded simultaneously to ERNA acquisition. RV contraction delays and amplitude were assessed using multiharmonic phase analysis of ERNA, and ventricular volumes and ejection fraction were assessed using gated blood-pool single photon emission computed tomography.
RVOT contraction was delayed in patients with BrS, and RV contraction heterogeneity increased according to the pattern of ST-segment elevation, without impairment of the amplitude of contraction. RV volumes were greater in patients with BrS compared with control subjects, without impairment of the ejection fraction, whatever the ST-segment elevation pattern or the magnitude of contraction heterogeneity.
In patients with BrS, we found a relationship between RV contraction heterogeneity and ST-segment pattern, providing evidence of a functional modulation of the arrhythmogenic substrate.
Abstract Background In patients with chronic angina-like chest pain, the probability of coronary artery disease (CAD) is estimated by symptoms, age, and sex according to the Genders clinical model. ...We investigated the incremental value of circulating biomarkers over the Genders model to predict functionally significant CAD in patients with chronic chest pain. Methods In 527 patients (60.4 years, standard deviation, 8.9 years; 61.3% male participants) enrolled in the European Ev aluation of In tegrated Cardiac I maging (EVINCI) study, clinical and biohumoral data were collected. Results Functionally significant CAD—ie, obstructive coronary disease seen at invasive angiography causing myocardial ischemia at stress imaging or associated with reduced fractional flow reserve (FFR < 0.8), or both—was present in 15.2% of patients. High-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST) levels, and high-sensitivity C-reactive protein (hs-CRP) were the only independent predictors of disease among 31 biomarkers analyzed. The model integrating these biohumoral markers with clinical variables outperformed the Genders model by receiver operating characteristic curve (ROC) (area under the curve AUC, 0.70 standard error (SE), 0.03 vs 0.58 SE, 0.03, respectively, P < 0.001) and reclassification analysis (net reclassification improvement, 0.15 SE, 0.07; P = 0.04). Cross-validation of the ROC analysis confirmed the discrimination ability of the new model (AUC, 0.66). As many as 56% of patients who were assigned to a higher pretest probability by the Genders model were correctly reassigned to a low probability class (< 15%) by the new integrated model. Conclusions The Genders model has a low accuracy for predicting functionally significant CAD. A new model integrating HDL cholesterol, AST, and hs-CRP levels with common clinical variables has a higher predictive accuracy for functionally significant CAD and allows the reclassification of patients from an intermediate/high to a low pretest likelihood of CAD.
Objectives The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography ...(SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD). Background Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking. Methods Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard99m Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader. Results Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular CV risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease SVD; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively). Conclusions SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography MCE to single photon emission computerized tomography ECG-GATED SPECT, at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease CAD in patients with suspect or known CAD using Coronary Angiography as Gold Standard–SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR )
Aortic valve stenosis progression rate is highly variable among patients and to date remains unpredictable. Evaluation of osteoblastic activity inside aortic valves may help identify patients with ...fast aortic stenosis progression rates and worse prognoses. Fluoride-18 sodium (FNa) is a clinically approved positron emission tomographic (PET) radiotracer with high and rapid bone uptake. The aim of this study was to test whether FNa accumulates in degenerative aortic valves and can be detected with PET imaging. Five patients with severe aortic stenosis and 10 patients free of aortic valvular calcium on computed tomography underwent PET imaging 40 minutes after the injection of 4 MBq/kg of FNa for oncologic or rheumatologic purposes. Maximal standard uptake values (SUVs) were measured retrospectively in aortic valves using PET imaging. Tissue-to-background ratios were calculated for each patient by dividing the maximal SUV measured in aortic valves by the mean SUV of blood. In patients with severe aortic stenosis, an intense accumulation of FNa was detected in aortic valve region on PET imaging, whereas only low activity was found in patients free of valvular calcification (median maximal SUV 2.6 g/ml/kg interquartile range (IQR) 2.3 to 3.6 vs 2.0 g/ml/kg IQR 1.7 to 2.2 and median tissue-to-background ratio 2.2 IQR 2.0 to 2.7 vs 1.5 IQR 1.5 to 1.7, respectively, p = 0.008 for both). Intraobserver variability for maximal SUV and tissue-to-background ratio in aortic valves was measured at 0.99 and interobserver variability at 0.98 and 0.97, respectively. In conclusion, in this pilot study, FNa accumulated in patients with severe aortic stenosis and could be quantified on PET imaging with good reproducibility. FNa PET imaging represents a promising imaging modality to evaluate osteoblastic activity inside calcified aortic valves.
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