(99m)Tc-HMDP scintigraphy rectifies wrong diagnosis of AL amyloidosis.

A 71-year-old African man without history of cardiac disease was referred to our center for dyspnea. Transthoracic echocardiogram and cardiac MRI were suggestive of cardiac amyloidosis (CA). The diagnosis of the light-chain cardiac amyloidosis (AL-CA) was made after a first endomyocardial biopsy. Accordingly chemotherapy was started. Systematic 99mTc-HMDP scintigraphy showed moderate cardiac uptake (visual score of 2), unusual for AL-CA, and permitted to rectify the diagnosis. Hereditary transthyretin cardiac amyloidosis was confirmed by a second endomyocardial biopsy with a positive Congo-red and anti-transthyretin antibody stainings, mass spectrometry and genetic analysis (Val122Ile mutation).

Masson's vegetant intravascular hemangioendothelioma in an external jugular vein aneurysm with recurrent thrombosis.

A 50-year-old male patient was admitted for a symptomatic aneurysm of the external jugular vein. Thrombosis of the aneurysm was treated by oral anticoagulant but recurrence of neck swelling and thrombosis occurred 1 year after oral anticoagulant was discontinued. No other vascular anomalies were detected, and blood tests were normal. Surgical resection was done "en bloc" with the muscular fibers in contact. Pathologic examination was compatible with a Masson's vegetant intravascular hemangioendothelioma. To our knowledge, this is the first case of symptomatic Masson's vegetant intravascular hemangioendothelioma diagnosed in a patient with thrombosed aneurysm of a cervical vein.

A New Three-Dimensional Echocardiography Method to Quantify Aortic Valve Calcification.

BACKGROUND: Aortic valve calcification (AVC) quantification is computed from multidetector computed tomography (MDCT). The aim of this study was to test the hypothesis that three-dimensional (3D) transthoracic echocardiography can be used to provide a bedside method to assess AVC. METHODS: The study included 94 patients (mean age, 78 ± 12 years; mean aortic valve [AV] area, 1.0 ± 0.6 cm2) referred for MDCT and echocardiography for AV assessment. Apical 3D full-volume data sets focused on the AV region were acquired during transthoracic echocardiography, and a region-growing algorithm was applied offline to compute 3D transthoracic echocardiographic AVC (AVC-3DEcho). AVC-3DEcho was compared with AVC by MDCT and with calcium weight in the subgroup of patients referred for surgery, with explanted AVs analyzed by a pathologist (n = 22). RESULTS: In the explanted valve group, AVC-3DEcho score exhibited fair correlations with MDCT score (r = 0.85, P < .001), calcium load (r = 0.81, P < .001), and peak AV velocity (r = 0.64, P < .001). In the overall population, AVC-3DEcho score correlated modestly with MDCT score (r = 0.61, P < .001) but had similar accuracy to identify severe aortic stenosis (area under the curve = 0.94). AVC-3DEcho > 1,054 mm3 identified severe aortic stenosis with specificity of 100% and sensitivity of 76%. In addition, AVC-3DEcho was associated with the presence of significant paravalvular regurgitation after transcatheter aortic valve implantation. Finally, intraobserver and interobserver variability for AVC-3DEcho score was 4.2% and 8.9%, respectively. CONCLUSIONS: AVC-3DEcho correlated with calcium weight obtained from pathologic analysis and MDCT. These data suggest that a bedside method for quantifying AV calcification with ultrasound is feasible.

Sequential cyclophosphamide-bortezomib-dexamethasone unmasks the harmful cardiac effect of dexamethasone in primary light-chain cardiac amyloidosis.

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients.

Causes and Consequences of Longitudinal LV Dysfunction Assessed by 2D Strain Echocardiography in Cardiac Amyloidosis.

OBJECTIVES: The aim of this study was to compare left ventricular longitudinal strain (LS) evaluated by 2-dimensional echocardiography with cardiac magnetic resonance (CMR) in cardiac amyloidosis (CA), establish correlations between histological and imaging findings, and assess the prognostic usefulness of LS measurement and CMR. BACKGROUND: CA is a condition with a poor prognosis due chiefly to 3 forms of amyloidosis: light-chain amyloidosis (AL), hereditary transthyretin (M-TTR), and wild-type transthyretin (WT-TTR). Two-dimensional echocardiography measurement of LS has been reported to detect early left ventricular systolic dysfunction. The pathophysiological underpinnings, regional distribution, and prognostic significance of LS in CA are unclear. METHODS: All patients underwent echocardiography, and 53 underwent CMR. The native hearts of the 3 patients who received heart transplants were subjected to histological examination. For each of the 17 left ventricular segments in the American Heart Association model, we evaluated LS, late gadolinium enhancement (LGE) by CMR, and cardiac amyloid deposition. Univariate and multivariate analyses were performed at 6 months to identify variables associated with major adverse cardiac events (MACE). RESULTS: We studied 79 patients with CA; 26 had AL, 36 M-TTR, and 17 WT-TTR. Mean LS was -10 ± 4%. Both LS and amyloid deposits showed a basal-to-apical gradient. The mean LS and number of segments with LGE were similar across the 3 CA types. LS correlated with LGE and amyloid burden (r = 0.72). LGE was seen in the 6 basal segments in all WT-TTR patients. During the median follow-up of 11 months (range 4 to 17 months), 36 (46%) patients experienced MACE. Independent predictors of MACE were apical LS (cutoff, -14.5%), N-terminal pro-B-type natriuretic peptide (cutoff, 4,000 ng/l), and New York Heart Association functional class III to IV heart failure. CONCLUSIONS: Basal-to-apical LS abnormalities are similar across CA types and reflect the amyloid burden. Apical LS independently predicts MACE.

Myocardial Gene Expression Profiling to Predict and Identify Cardiac Allograft Acute Cellular Rejection: The GET-Study.

AIMS: Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. METHODS: A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or ≥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ≥3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10). RESULTS: We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples. CONCLUSION: Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipients' care.

[Cardiac amyloidosis: How to recognize them and manage them?] / Les amyloses cardiaques : les reconnaître et les prendre en charge.

Cardiac amyloidosis must be suspected in all cases of hypertrophic cardiomyopathy with preserved left ventricular ejection fraction to allow specific management. Final diagnosis needs pathological evidence, but bone scintigraphy may be an alternative for TTR amyloidosis. Invasive samplings are limited by new tools. Amyloidosis typing is required to start specific therapies if possible. Main specific treatments that are available are chemotherapy for AL; transthyretin stabilizer or gene therapy, studied for TTR-related cardiac amyloidosis.

[Senile systemic amyloidosis: definition, diagnosis, why thinking about?]. / Amylose systémique sénile : définition, diagnostic, pourquoi y penser ?

Senile systemic amyloidosis (SSA) is characterized by infiltration of amyloid transthyretin fibrils in the myocardium. SSA occurs mainly (but not always) in elderly men. SSA leads to hypertrophic and/or restrictive cardiomyopathy complicated by conduction disturbances, atrial arrhythmia and systemic embolization (stroke…). That is why SSA needs a special care and to be diagnosed. Cardiac SSA diagnosis needs to exclude two other forms of cardiac amyloidosis: AL amyloidosis (light chain) and hereditary transthyretin amyloidosis (genetic testing). Scintigraphic 99mTc-DPD heart retention is observed in cardiac amyloidosis. DPD heart retention is more frequent in cardiac transthyretin amyloidosis than in cardiac AL amyloidosis. Specific treatments of cardiac TTR amyloidosis are in development.