Usefulness of 99mTc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis

Background: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges.

Objective: To assess the diagnostic accuracy of ^99mTc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes.

Methods: 121 patients with suspected CA underwent ^99mTc-HMDP-scintigraphy in addition to standard investigations.

Results: CA was diagnosed in all AL (n?=?14) and wt-TTR (n?=?21). Among m-TTR (n?=?34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. ^99mTc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score?≥?2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR?>?1.94 predicted acute heart failure and/or death.

Conclusions: This preliminary study suggests that ^99mTc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs. ^99mTc-HMDP-scintigraphy appears to provide prognostic information in CA.     

Echography and scintigraphy using technetium 99m pyrophosphate in the diagnosis of cardiac amyloidosis

The diagnosis of amyloid cardiomyopathy was only based, until the last few years, on the results of invasive techniques. It seems presently that the combined contribution of cardiac sonography and scintigraphy using technetium 99m pyrophosphate, makes, most of the time, this diagnosis possible without need for additional examinations. This notion is illustrated by a typical case-report and data from the literature. Demonstration on the cardiac sonogram of a thickening of the walls-while the context and especially the electrocardiogram are not in favor of a left ventricular hypertrophy--associated with a very particular "hyperechoing" aspect and an abnormal fixation on the scintigram, may be considered specific of this disease.     

Noninvasive diagnosis of biopsy-proven cardiac amyloidosis

OBJECTIVES: This study analyzed the utility of electrocardiographic (ECG) and echocardiographic findings in the diagnosis of amyloidosis proven by endomyocardial biopsy. BACKGROUND: Cardiac amyloidosis is associated with characteristic ECG and echocardiographic changes, yet each finding alone is relatively nonspecific. A combination of noninvasive prognostic parameters would be desirable for this tissue-based diagnosis. METHODS: We performed an analysis of 196 consecutive patients referred for endomyocardial biopsy because of clinical suspicion of cardiac amyloidosis. The diagnosis was confirmed in 58 patients (29%). The ECGs, echocardiograms, and right heart hemodynamic data were reviewed to determine which findings strongly correlate with the diagnosis. These findings were then used to build multivariate logistic regression models that predict the log-odds of having cardiac amyloidosis. RESULTS: The univariate analysis showed that low-voltage and pseudo-infarction patterns on the ECG and increased myocardial thickness and speckled-appearing myocardium on the echocardiogram were associated with biopsy-proven cardiac amyloidosis (each p < 0.01). In multivariate logistic regression models, a combination of a low voltage and measures of myocardial thickness produced the most statistically useful models. For instance, one model showed that if a low voltage was present and interventricular septal thickness is >1.98 cm, the diagnosis of cardiac amyloidosis could be made with a sensitivity of 72% and a specificity of 91%. In this model, the positive predictive and negative predictive values were 79% and 88%, respectively. CONCLUSIONS: In patients with suspected cardiac amyloidosis, a combination of noninvasive parameters-namely, a low voltage and increased intraventricular septal thickness-is a useful diagnostic tool.     

Is technetium-99 m-pyrophosphate scintigraphy valuable in the diagnosis of cardiac amyloidosis?

Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloid fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.     

99mTc-HSA-D scintigraphy in the diagnosis of protein-losing gastroenteropathy due to secondary amyloidosis

Secondary amyloidosis frequently involves the gastrointestinal tract and may result in ulceration, hemorrhage, and protein-losing enteropathy. We report a patient with severe hypoalbuminemia in whom endoscopy revealed widespread ulceration of the small intestine. The protein-losing site was detected by^99mTc-diethylene triamine pentaacetic acid human serum albumin (^99mTc HSA-D) scintigraphy. This evidence suggests that the ulcers and mucosal lesions associated with amyloidosis contribute to abnormal protein loss from the gastrointestinal tract.     

Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis

Background and aim: Radio‐labelled Aprotinin has been shown to bind with amyloid fibrils in vitro as well as in vivo. The aim was to test the usefulness of ^99mTc‐Aprotinin imaging in systemic amyloidosis. Methods: Thirty‐five cases who had ^99mTc‐Aprotinin scans for the assessment of systemic amyloidosis were reviewed retrospectively. Eighteen had biopsy‐proven amyloidosis and 17 were controls (amyloidosis was excluded by negative biopsies and non‐invasive tests). Five of 18 patients with amyloidosis had final diagnosis of cardiac amyloid. Results: Physiological uptake of ^99mTc‐Aprotinin was noted in the urinary tract (kidneys and bladder) and in the liver of all patients and controls; and non‐specific uptake of ^99mTc‐Aprotinin was visualised in the spleen and oro‐facial structures in the majority of both groups. Myocardial ^99mTc‐Aprotinin uptake was noted in all five patients with final diagnosis of cardiac amyloidosis and in none of the 30 subjects who did not have cardiac amyloid. The median heart to background uptake ratio was 2.0 in cardiac amyloid patients and 1.1 in subjects without cardiac amyloid (P = 0.0004). Single Photon Emission Tomography (SPECT) studies of the thorax confirmed that the site of uptake lay within the myocardium. In the amyloidosis group, site‐specific ^99mTc‐Aprotinin uptake was also identified in the subcutaneous tissue of the legs and in a breast nodule shown to be positive for amyloidosis on biopsy. Conclusions: ^99mTc‐Aprotinin imaging may be a useful non‐invasive method for the assessment of the presence and extent of extra‐abdominal amyloid, particularly cardiac amyloidosis. It has little role in diagnosis of amyloidosis involving the oro‐facial and abdominal structures.     

Noninvasive detection of active pericardial bleeding using cardiac blood pool scintigraphy

The diagnosis of active pericardial bleeding has traditionally depended on an invasive documentation by needle aspiration, angiography, or direct inspection. Blood pool scintigraphy performed in 2 patients just before and after the development of hemopericardium revealed unique images in which acute pericardial bleeding manifested itself by an additional blood pool adjacent to the cardiac chambers. With appropriate attention to technical factors, such distinctive images should be highly specific for active bleeding into the pericardial sac.     

99mTechnetium-labeled cardiac scintigraphy for suspected amyloidosis: a review of current and future directions

Heart Failure Reviews - Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality...     

Non-invasive assessment of the presence and severity of cardiac amyloidosis. A study in familial amyloidosis with polyneuropathy by cross sectional echocardiography and technetium-99m pyrophosphate scintigraphy.

Of two infants with congenital cardiac diverticula one had a defect consisting of a submitral valvular diverticulum rather than the expected aneurysm. It was clearly shown by echocardiography as well as angiography and was associated with moderate mitral incompetence and a poorly functioning left ventricular wall. The second infant had an isolated apical left ventricular diverticulum with subnormal left ventricular function and severe mitral incompetence. Because of intractable congestive heart failure this infant underwent successful replacement of a dysplastic fibrotic mitral valve which on histological examination had myxomatous features. The association between congenital mitral disease and congenital apical diverticular may be related to race and sex.     

False positive technetium-99m pyrophosphate scintigraphy in a patient with cardiac amyloidosis light chain: Case report

Introduction:Patients with cardiac amyloidosis light chain (AL) present with negative Tc-99m pyrophosphate (PYP) scintigraphy (absent or mild heart uptake). On the contrary, patients with cardiac amyloidosis transthyretin (ATTR) present with positive Tc-99m PYP scanning (intensive heart uptake). We present a false positive Tc-99m PYP scintigraphy (grade 2, the heart-to-contralateral ratio is 1.65) in a patient with AL.Patient concerns:A 42-year-old Chinese man complained of effort intolerance, chest discomfort, and short of breath progressively over 1 year. New York Heart Association Class III. Physical examination showed legs swelling. Laboratory revealed elevated brain natriuretic peptide of 23,031 ng/mL (0–88) and Troponin-T of 273.4 ng/mL (0–14).Diagnosis:Cardiac amyloidosis light chain. Evidences: free light chains (FLCs): decreased serum free kappa/lambda ratio of 0.043 (0.31–1.56). Immunofixation electrophoresis: a positive lambda light chain monoclonal protein. Cardiac biopsy: HE: Ambiguity Congo red strain. Myocardial immunofluorescence: positive lambda light chain. Myocardial immunohistochemistry: positive lambda light chain, negative kappa light chain, and TTR.Interventions:Furosemide 40 mg qd, torasemide 20 mg qd, spirolactone 20 mg qd, potassium chloride 10 mL per 500 mL urine, atorvastatin calcium tablet 20 mg qd, aspirin enteric-coated tablets 100 mg qd during the 2-weeks in-hospital.Outcomes:The patient died 2 months later after discharge.Conclusion:False positive Tc-99m PYP scintigraphy may rarely presented in patients with cardiac amyloidosis light chain. So, the clonal plasma cell process based on the FLCs and immunofixation is a base to rule out AL cardiac amyloidosis when we interpret a positive Tc-99m PYP scintigraphy.     

Noninvasive diagnosis of small bowel Crohn's disease: combined use of bowel sonography and Tc-99m-HMPAO leukocyte scintigraphy

BACKGROUND: Crohn's disease (CD) is frequently localized in the small bowel, with the diagnosis of disease and the assessment of its extension made by ileo-colonoscopy (IC) and small bowel enteroclysis (SBE). Transabdominal bowel sonography (BS) and Tc-99m-HMPAO leukocyte scintigraphy (LS) are increasingly used for the diagnosis of CD because of their minimal invasiveness, reproducibility, and acceptable costs. METHODS: From March 2000 to July 2003, we performed IC, SBE, BS, and LS in 84 patients with either suspected or known small bowel CD. RESULTS: Small bowel CD was present in 50 patients, whereas the other 34 patients received a different diagnosis. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were, respectively, 98%, 97%, 98%, 97%, and 0.97 for SBE; 92%, 97%, 98%, 88%, and 0.94 for BS; and 90%, 93%, 96%, 85%, and 0.92 for LS. In addition, the combined use of BS and LS led to overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 100%, 93%, 96%, 100%, and 0.97, respectively. BS showed a fair concordance with SBE in terms of location (k = 0.71) and a correlation with the extension of the disease (r = 0.67, P < 0.001). LS showed a concordance with SBE with regard to location in about one-half the population (k = 0.54), whereas it was less effective than SBE in defining disease extension. CONCLUSIONS: BS and LS are 2 accurate techniques for the diagnosis of small bowel CD, and their combined use can be recommended as an early diagnostic approach to patients in which the disease is suspected. SBE remains the best procedure for the definition of the location and extension of the disease.     

淀粉样变心肌病的诊断思路

目的:通过对淀粉样变心肌病的临床分析以探讨该病早期诊断的方法.方法:回顾性分析8例原发性淀粉样变心肌病患者的临床特征、心电图及超声心动图表现、确诊方法和预后.结果:临床表现为心力衰竭患者7例,其中右心力衰竭4例,全心力衰竭3例;既往高血压而表现为低血压5例;舌大5例.心电图示:肢体导联低电压6例,其中5例并发前胸导联R波进展不良和ST-T改变.超声心动图示:所有患者均表现有左心室大小正常,左心房明显增大,室间隔和左室壁均明显增厚伴室壁运动弥漫性减弱.8例患者经心内膜下心肌或舌肌取材,通过苏木精-伊红和刚果红染色,均为阳性.平均随访(23.6±11.3)个月,8例患者均死亡.结论:淀粉样变性是一种系统性疾病,并发心肌病变患者有以下临床特征:①心室腔不大伴进行性难治性心力衰竭,②左心室肥厚伴心电图低电压,③既往有高血压伴进行性低血压及类似陈旧性心肌梗死心电图图形,④左室壁均匀肥厚伴室壁活动弥漫性减低,⑤舌体宽大肥厚;通过心内膜心肌或心外组织活检和组织化学染色可以确诊.