Myocardial Amyloidosis: The Exemplar Interstitial Disease

Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart failure, and it is the imaging modality that most often raises the suspicion of cardiac amyloidosis. Echocardiography can provide an assessment of the likelihood of cardiac amyloid infiltration versus other hypertrophic phenocopies and can assess the severity of cardiac involvement. Visualizing myocardial amyloid infiltration is challenging and, until recently, was restricted to the domain of the pathologist. Two tests are transforming this: cardiac magnetic resonance (CMR) imaging and bone scintigraphy. After the administration of contrast, CMR is highly sensitive and specific for the 2 main types of ventricular myocardial amyloidosis, light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). CMR structural and functional assessment combined with tissue characterization can redefine cardiac involvement by tracking different disease processes, ranging from amyloid infiltration, to the myocardial response associated with amyloid deposition, through the visualization and quantification of myocardial edema and myocyte response. Bone scintigraphy (paired with exclusion of serum free light chains) is emerging as the technique of choice for distinguishing ATTR from light chain cardiac amyloidosis and other cardiomyopathies; it has transformed the diagnostic pathway for ATTR, allowing noninvasive diagnosis of ATTR without the need for a tissue biopsy in the majority of patients. CMR with tissue characterization and bone scintigraphy are rewriting disease understanding, classification, and definition, and leading to a change in patient care.     

Cardiac amyloidosis causing ventricular tachycardia. Diagnosis made by endomyocardial biopsy

In patients with malignant ventricular arrhythmias, endomyocardial biopsy may be helpful when all other findings from the workup are negative. A case of nonsustained polymorphic ventricular tachycardia is presented. The findings from an echocardiogram, coronary angiogram, and cardiac catheterization were negative. An electrophysiologic study showed inducible nonsustained ventricular tachycardia. A right ventricular endomyocardial biopsy was diagnostic of cardiac amyloid. The findings from a workup for systemic amyloidosis were negative. Primary cardiac amyloidosis should be considered in patients with malignant arrhythmias and no documented heart disease, and endomyocardial biopsy is helpful in making this diagnosis.     

Uhl's disease: An uncommon presentation of a rare disease

Uhl's disease, also known as Uhl anomaly, is a rare disease secondary to selective but uncontrolled apoptosis of right ventricular myocytes during the perinatal period, after complete cardiac development, leading to the absence of right ventricular myocardium and the direct apposition of endocardium to epicardium without a myocardial layer in between, resulting in right ventricular failure.The present paper describes a case of Uhl's disease with an uncommon presentation. A 28-year-old man was admitted with dyspnea and cyanosis. Transthoracic echocardiography showed severe dilation of the right chambers, impaired right ventricular systolic function and a large ostium secundum atrial septal defect (ASD). Cardiac catheterization revealed pulmonary hypertension, with increased pulmonary capillary wedge pressure (mean 19 mmHg) and Qp:QS 0.88:1. At this point, the authors considered that a main diagnosis of ASD could not explain the clinical features and hemodynamic data. A primary disease of the right ventricle was the most likely hypothesis and cardiac magnetic resonance imaging was performed, which demonstrated an extremely thin-walled right ventricle, with almost complete absence of right ventricular free wall myocardium, compatible with Uhl's disease.     

Revisiting Non-Compaction Cardiomyopathy Through a Case with Cyanosis and Complete Heart Block

Left ventricular non-compaction or “spongy myocardium”, is a rare congenital cardiomyopathy that should be considered as a possible diagnosis because of its potential complications. Echocardiography is the diagnostic tool of choice, and cardiomagnetic resonance (CMR) can confirm or rule out this disease. Herein, we report the case of an 8-month-old female child who presented with congestive cardiac failure (CCF) and symptomatic complete heart block (CHB). An echocardiogram established the diagnosis as non-compaction cardiomyopathy (NCCM). An associated double outlet right ventricle with ventricular septal defect and valvular pulmonary stenosis was found. Cardiac magnetic resonance study confirmed the findings. This singular case report of NCCM highlights the importance of clinical awareness of this rare abnormality, its varied presentation and associated cardiac anomalies. The article revisits NCCM and focuses on the practical issues for a proper echodiagnosis.     

伴心肌肌钙蛋白I持续升高和心绞痛症状的系统性淀粉样变性

系统性淀粉样变性相对少见,累及心脏时,可出现多种临床表现,极易造成误诊和漏诊。本例报道了一位66岁女性,表现为持续性肌钙蛋白I升高和反复发作的胸痛,根据心脏影像学检查,结合单克隆免疫球蛋白试验及骨髓细胞学和骨髓活检,最终诊断为“系统性淀粉样变性（心脏受累）”。因此,对于射血分数保留的不能解释原因的心衰、肌钙蛋白升高、心脏影像学异常或存在系统性疾病,均应警惕有无淀粉样变可能。     

Cardiac Amyloidosis Mimicking Hypertrophic Cardiomyopathy

ABSTRACT. Amyloid infiltration of the heart may frequently masquerade as other cardiac disorders. The extended use of echocardiography may contribute to an erroneuous diagnosis of hypertrophic cardiomyopathy, as both conditions show several features in common. This was the case with the patient reported below. A low QRS amplitude, an increased right ventricular wall thickness, thickened cardiac valves, and a pericardial effusion may, however, indicate amyloid infiltration. The diagnosis of systemic amyloidosis of immunocytic origin was subsequently established in our patient. A definitive diagnosis of amyloid heart disease requires endomyocardial biopsy, but it is suggested that typical noninvasive findings together with demonstration of amyloid in an organ other than the heart is sufficient for a reliable diagnosis. In addition, systemic manifestations may contribute to a correct diagnosis in generalized amyloidosis. Our patient had features consistent with the rare muscle pseudohypertrophy syndrome, which is associated with immunocytic amyloidosis.     

The functional defect in amyloid heart disease. The "stiff heart" syndrome.

Left ventricular performance was studied in three patients with heart failure due to amyloid deposits. The diagnosis of amyloidosis was proved by cardiac biopsy in two patients and by rectal biopsy in the third. One patient had myelomatosis, but the other two had no other identifiable disease. The investigative technique allowed simultaneous measurements of pressure and volume in the left ventricle. The functional defect with slow cardiac filling at high pressure and greatly reduced left ventricular contraction differed from that of constrictive pericarditis and other heart muscle disease. These features of a "stiff heart" are probably unique to amyloidosis and should make possible positive recognition of the condition on the basis of echocardiographic, angiographic and hemodynamic findings.     

Familial and primary (AL) cardiac amyloidosis: echocardiographically similar diseases with distinctly different clinical outcomes.

OBJECTIVE: To determine whether patients with myocardial amyloidosis due either to AL (primary) amyloid or familial amyloid have distinguishing echocardiographic or electrocardiographic features; and to compare the prevalence of heart failure and survival in the two types of amyloidosis in relation to echocardiographic findings. DESIGN: Blinded group comparison of randomly selected cases of cardiac amyloidosis. SETTING: International referral centre for amyloid research and treatment. PATIENTS: 36 patients with cardiac amyloid heart disease, of whom 12 had familial and 24 had primary AL amyloidosis. RESULTS: Familial and AL echocardiograms were morphologically indistinguishable, with similar left ventricular wall thickness, mean (SD) 15.4 (2.3) nu 15.8 (2.5) mm, respectively; right ventricular wall thickness was also similar between amyloid types: 9.6 (2.8) nu 9.7 (6.5) mm, respectively. Doppler indices of left and right ventricular function, left ventricular volume, and ejection fraction were also similar. Low voltage electrocardiograms (< 0.5 mV) were more common in the AL (16/24, 67%) than in the familial group (4/12, 25%), P < 0.05. The one year survival for familial and AL forms was 92% (11/12) nu 38% (6/24), respectively, with virtually all deaths due to cardiac causes. CONCLUSIONS: Although cardiac involvement is echocardiographically indistinguishable, cardiac mortality is very different between the two forms of amyloidosis. Preservation of electrocardiographic voltage in familial amyloidosis suggests that the particular biochemical characteristics of distinct types of amyloid fibril have different pathological effects on the myocardium. This distinction becomes critical in the evaluation, treatment, and management of patients who have a diagnosis within the spectrum of the protein deposition diseases.     

Magnetic resonance imaging in hypertrophied left ventricular myocardium due to amyloidosis

The certain diagnosis of cardiac amyloidosis is only possible with myocardial biopsy, even if echocardiographic studies often show a typical sparkling pattern. Using magnetic resonance imaging (MRI) we examined if there is a specific morphological pattern in patients with amyloidosis compared with patients with hypertrophic cardiomyopathy (LVH). With a 1.0 T magnetom and FISP 2D sequences two patients with biopsy-proven cardiac amyloidosis (AL), two patients with generalized AL and suspected cardiac AL, and five patients with LVH were examined and data were compared with echocardiography. In two cases with cardiac AL, contrast medium (Gd-DTPA) was given and dynamic-turbo-flash-sequences were obtained. In patients with AL, both ventricles were hypertrophied, whereas in the cases of hypertrophy due to other reasons only the left ventricle was hypertrophied. The systolic wall thickening was in all cases of amyloidosis below 30%. In contrast to echocardiography, a myocardial sparkling pattern in amyloidosis was not found with MRI. Even with additional contrast examination we could not differentiate the types of hypertrophy by imaging solely the left ventricular wall. There is no specific myocardial pattern in cardiac amyloidosis neither in standard MRI nor after examination with additional contrast medium, but concomitant right ventricular (RV) and left ventricular (LV) hypertrophy is a typical observation in these patients.Presented at the 37th Annual World Congress, International College of Angiology, Cologne, Germany, June 1996.     

Results of endomyocardial biopsy in patients with spontaneous ventricular tachycardia but without apparent structural heart disease

To evaluate possible occult myocardial disease in 18 patients whose only major manifestation of heart disease was spontaneous ventricular tachycardia or fibrillation, right ventricular endomyocardial biopsies were performed. None of the patients had symptoms of ischemic or congestive heart disease, and at catheterization none had significant lesions of the coronary arteries or regional wall motion abnormalities of the left ventricle. The mean left ventricular ejection fraction (65 +/- 7%), mean right ventricular ejection fraction (55 +/- 9%), mean cardiac index (3.0 +/- 0.5 1/min/m2), mean right atrial pressure, mean pulmonary capillary wedge pressure, and mean pulmonary artery systolic pressure were normal. However, right ventricular endomyocardial biopsy specimens were abnormal in 16 of 18 (89%) patients: nine (50%) had changes of a significant, although nonspecific, cardiomyopathy with myocellular hypertrophy, interstitial and perivascular fibrosis, and vascular sclerosis; three (17%) had subacute inflammatory myocarditis; two (11%) had diffuse abnormalities of the intramyocardial arteries; and two (11%) had pathologic changes consistent with arrhythmogenic right ventricular dysplasia. In the two (11%) patients with normal biopsy specimens, one had Wolff-Parkinson-White syndrome and the other had mitral valve prolapse. Although histologic abnormalities were found in 89% of these patients, performance of right ventricular endomyocardial biopsies in this group of patients should be considered a research procedure. We conclude that the majority of patients who have serious ventricular arrhythmias but no apparent structural cardiac abnormalities have abnormal right ventricular biopsy specimens and that the arrhythmias may be the first manifestation of a variety of primary myocardial abnormalities.     

Early manifestation of myocardial involvement in systemic sclerosis

IntroductionSystemic sclerosis (SSc) is a systemic autoimmune disease involving multiple organs. We present a rare case of SSc in which clinical manifestations of cardiac fibrosis occurred early in the disease course.Case reportWe report the case of a 40-year-old Caucasian man, previously diagnosed with SSc, who presented with decompensated heart failure. Transthoracic echocardiography was remarkable for severe right ventricular systolic dysfunction, abnormal ventricular septal motion, severe functional tricuspid regurgitation and normal pulmonary artery systolic pressure. Left ventricular ejection fraction was 45%. Right heart catheterization revealed no signs of pulmonary hypertension. Cardiac magnetic resonance (CMR) showed diffuse myocardial infiltration, later confirmed as myocardial fibrosis by endomyocardial biopsy.ConclusionsMyocardial fibrosis is an important cause of early heart failure in SSc patients and is associated with poor prognosis. Echocardiography and CMR help establish the diagnosis and enable an appropriate therapeutic strategy to be developed in such cases.     

Antimyosin antibody cardiac imaging: its role in the diagnosis of myocarditis

Right ventricular endomyocardial biopsy currently remains the procedure of choice for identifying patients with symptomatic heart failure due to myocarditis from the larger population with idiopathic dilated cardiomyopathy. Despite its specificity, the sensitivity of right ventricular biopsy remains uncertain because of the focal or multifocal nature of the disease. Because myocyte necrosis is an obligate component of myocarditis, the use of indium-111 antimyosin imaging was evaluated in 82 patients with suspected myocarditis. Seventy-four patients had dilated cardiomyopathy of less than 1 year's duration (mean left ventricular ejection fraction 0.30 +/- 0.02); eight patients had normal left ventricular function (mean ejection fraction 0.59 +/- 0.03). Symptoms at presentation included congestive heart failure (92%), chest pain mimicking myocardial infarction (6%) and life-threatening ventricular tachyarrhythmias (2%). All patients underwent planar and single photon emission computed tomographic (SPECT) cardiac imaging after injection of indium-111-labeled antimyosin antibody fragments and right ventricular biopsy within 48 h of imaging. Antimyosin images were interpreted as either abnormal or normal and correlated with biopsy results. On the basis of the right ventricular histologic examination, the sensitivity of antimyosin imaging was 83%, specificity 53% and predictive value of a normal scan 92%. Improvement in left ventricular function occurred within 6 months of treatment in 54% of patients with an abnormal antimyosin scan compared with 18% of those with a normal scan (p less than 0.01). Antimyosin cardiac imaging may be useful for the initial evaluation of patients with dilated and nondilated cardiomyopathy and clinically suspected myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is diagnostic myocardial biopsy useful in the XXI century?

BACKGROUND: Progress in non-invasive diagnostic techniques such as ultrasonography, computerised tomography or magnetic resonance caused a significant decrease in the use of diagnostic myocardial biopsy (DMB). However, recent advances in molecular biology and widening knowledge about the role of new biochemical markers gives hope for more detailed assessment of cardiomyocyte pathophysiology, based on the proper examination of myocardial biopsy specimen. AIM: To assess current usefulness of DMB in the diagnosis of various myocardial disorders and monitoring after heart transplantation. METHODS: DMB was performed in 104 patients (84.6% males) with a clinical diagnosis of idiopathicdilated cardiomyopathy (35.6%), post-inflammatory dilated cardiomyopathy (22.1%), restrictive cardiomyopathy (2.9%), post-infarction myocardial injury (17.3%), ventricular arrhythmias resistant to treatment (2.9%), cardiac tumour (0.96%), suspected arrhythmogenic right ventricular dysplasia (0.96%) and with transplanted heart (17.3%). In each patient 3-4 specimens of the right ventricular cardiac muscle were taken. Immunohistochemical reactions were used to assess the presence of desmin. Myocarditis was diagnosed on the basis of morphological assessment of specimens stained with HE, Mallory trichome and immunohistochemical methods which identified lymphocytes T (CD3, OPD 4, UCHL1), endothelium (CD34) and antigen MHC II (DP, QR). In addition, specimens suggesting laminopathy or amyloidosis were examined under electron microscope. RESULTS: DMB revealed the absence of desmin (19.2%), abnormal concentration of desmin (21.1%), myocarditis (19.2%), so-called vascular myocardial injury (16.3%), other proteinopathies (2.3%), amyloidosis (1.9%), connective tissue diseases (0.96%), arrhythmogenic right ventricular dysplasia (0.96%), toxic injury (0.96%) and normal myocytes (0.96%). CONCLUSIONS: Our results suggest that complex analysis of myocardial biopsy specimen provides detailed information of the pathogenesis of cardiac disorders. However, further progress in molecular biology is needed to achieve more complete diagnosis.     

Magnetic Resonance Imaging in Chronic Chagas' Disease: Correlation with Endomyocardial Biopsy Findings and Gallium-67 Cardiac Uptake

BACKGROUND: We studied the correlation among cardiac magnetic resonance imaging (MRI), gallium-67 myocardial uptake, and right ventricular endomyocardial biopsy results in chronic Chagas' disease. To our knowledge, this represents the first attempt to correlate the histological findings with cardiac MRI and gallium-67 myocardial uptake for noninvasive diagnosis of inflammatory activity associated with Chagas' disease. METHODS: Ten male patients with cardiomyopathy secondary to Chagas' disease were studied (mean age, 47.7 +/- 7 years; congestive heart failure New York Heart Association [NYHA] functional class II [two patients], III [six patients], and IV [two patients]; and mean echocardiographic left ventricular [LV] ejection fraction [EF], 36 +/- 6%). The patients underwent right ventricular endomyocardial biopsy, cardiac MRI, and gallium-67 myocardial uptake testing. The results of this group were compared with those of a control group of patients with idiopathic dilated cardiomyopathy who were matched in age (mean age, 46 +/- 10 years), LV function (mean echocardiographic EF, 30 +/- 4%), and NYHA classification (one patient in class II, five patients in class III, and one patient in class IV). RESULTS: All patients with Chagas' disease showed higher signal intensity on MRI after the administration of gadolinium. The intensity of the septal signal changed from 0.90 +/- 0.11 to 1.56 +/- 0.19 (P < 0.001). In the control group, there was no difference in signal intensity with gadolinium (mean septal intensity, 0.94 +/- 0.12 before and 0.99 +/- 0.15 after; NS). On biopsy, eight chagasic patients had evident signs of myocarditis, and two patients had borderline evidence myocarditis. However, only one patient in the control group had a histological diagnosis of borderline myocarditis. Gallium-67 cardiac uptake was positive for myocardial inflammatory process in seven chagasic patients and borderline in one. On the other hand, only one patient in the control group had an uptake that was positive for inflammation, and one had a borderline result. CONCLUSIONS: In conclusion, the data from this study strongly suggest that myocarditis is frequently found in Chagas' disease. Cardiac MRI appears to be an accurate and alternative method for the diagnosis of inflammatory process associated with Chagas' disease.     

Wild type transthyretin cardiac amyloidosis in a young individual: A case report

Rationale:Senile systemic amyloidosis, a disease of elderly is caused by amyloid deposition of wild-type transthyretin. The symptoms often overlap with other heart diseases. Hence it is either misdiagnosed or considered as a normal aging process in majority of cases.Patient concerns:We present a young patient of wild-type transthyretin amyloidosis, contradicting its only senile presence. The 34-year-old man presented with dyspnoea on exertion. He was suffering from hypertension for consecutive 3 years.Diagnosis:Echocardiography demonstrated left ventricular hypertrophy with reduced global longitudinal strain and apical sparing. Congo red staining and immuno-histochemical staining of the abdominal fat biopsy confirmed transthyretin amyloid deposition. Genetic analysis revealed absence of any mutant variant/s of transthyretin gene, confirming wild-type transthyretin amyloidosis.Intervention:A combination of amlodipine 5 mg, telmisartan 40 mg, and chlorthalidone 12.5 mg once daily was given to control the blood pressure of the patient.Outcome:Blood pressure was controlled but he continued to have exertional dyspnoea. The patient expired in December 2019.Lessons:A systematic diagnosis for wild type transthyretin amyloid cardiomyopathy (ATTR-CM) shall be considered in young cardiac patients suffering from cardiac distress with unknown etiology.     

Diagnosis and management of patients with left ventricular hypertrophy: Role of multimodality cardiac imaging. A scientific statement of the Heart Failure Association of the European Society of Cardiology

Left ventricular (LV) hypertrophy consists in an increased LV wall thickness. LV hypertrophy can be either secondary, in response to pressure or volume overload, or primary, i.e. not explained solely by abnormal loading conditions. Primary LV hypertrophy may be due to gene mutations or to the deposition or storage of abnormal substances in the extracellular spaces or within the cardiomyocytes (more appropriately defined as pseudohypertrophy). LV hypertrophy is often a precursor to subsequent development of heart failure. Cardiovascular imaging plays a key role in the assessment of LV hypertrophy. Echocardiography, the first-line imaging technique, allows a comprehensive assessment of LV systolic and diastolic function. Cardiovascular magnetic resonance provides added value as it measures accurately LV and right ventricular volumes and mass and characterizes myocardial tissue properties, which may provide important clues to the final diagnosis. Additionally, scintigraphy with bone tracers is included in the diagnostic algorithm of cardiac amyloidosis. Once the diagnosis is established, imaging findings may help predict future disease evolution and inform therapy and follow-up. This consensus document by the Heart Failure Association of the European Society of Cardiology provides an overview of the role of different cardiac imaging techniques for the differential diagnosis and management of patients with LV hypertrophy.     

Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality

Background

Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction.

Objective

To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality.

Methods

A total of 1959 reports of “infarct size” were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors – left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named “MET-AMI”. The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees.

Results

The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%). Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047), ventricular dysfunction (p = 0.0005) and infarcted size (p = 0.0005); the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003).

Conclusion

The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently associated with long-term mortality, especially for ischemic heart disease death.     

Le diagnostic de l’amylose cardiaque par résonance magnétique : les éléments discriminants

Infiltrative cardiomyopathies refers to deposits of substances in the myocardial tissue resulting in a structural abnormality and/or alteration of cardiac function. Cardiac amyloidosis is an extracellular infiltration of amyloid fibril. Cardiac magnetic resonance imaging (MRI) is essential (in the) for its diagnosis. MRI sequences (morphological, viability and parametric mapping) allow a structural and dynamic analysis of the cardiac function as well as a characterization of the myocardial tissue: edema, fatty infiltration, fibrosis. In cardiac amyloidosis, the morphological sequences classically highlight ventricular hypertrophy and thickening of the heart valves. Ventricular functions are assessed by the cine sequences (The cine sequences make it possible to evaluate the ventricular functions.) The viability sequences show (a more diffuse distribution of hypersignals) an abnormal pattern of late gadolinium enhancement in both circumferential and sub-endocardial distribution. The relaxometry sequences or parametric T1 and/or T2 mapping allow the spatial visualization of quantitative changes of the myocardium. The presence of macroscopic myocardial edema or fibrosis causes a prolongation of the native T1 and an increase of the extracellular volume.     

Idiopathic restrictive cardiomyopathy in the young: report of two cases

Two cases of idiopathic restrictive cardiomyopathy in young age are reported. This rare kind of restrictive cardiomyopathy is characterized by the absence of specific histologic features of myocardial abnormalities. In both cases (aged 12 and 9 years at diagnosis), the clinical picture was characterized by severe and slowly progressive congestive heart failure. The electrocardiogram showed biventricular hypertrophy, right bundle branch block and pseudoinfarctional Q waves. Echocardiography revealed moderate pericardial effusion, biatrial enlargement, and normal or nearly normal biventricular dimensions and systolic function. Cardiac catheterization disclosed the typically restrictive filling pattern. Right ventricular endomyocardial biopsy demonstrated moderate interstitial fibrosis and cellular hypertrophy without any evidence of infiltrative or storage myocardial disease or endocardial pathology. One patient underwent cardiac transplantation, whereas in the other, transplantation was contraindicated because of longstanding pulmonary hypertension and liver cirrhosis. The knowledge of this rare entity may correctly orient the diagnostic process in children suspected of having restrictive myocardial disease. Heart, or even heart-lung, transplantation must be considered in cases with congestive heart failure before irreversible damage occurs in many organs.     

Cardiac Amyloidosis: Evolving Approach to Diagnosis and Management

The systemic amyloidoses are a group of heterogeneous disorders characterized by extracellular deposition of misfolded fibrillar protein that results in organ dysfunction. Involvement of the heart (cardiac amyloidosis) is manifest by increased cardiac wall thickness and impairment of myocardial diastolic and systolic properties, changes that result in heart failure, dysrhythmia, and death. Amyloidosis is classified by precursor protein, with light-chain (AL) and transthyretin (TTR) disease being most common in the United States. TTR amyloid can result from misfolding of variant TTR, a genetically inherited disease, or wild-type TTR, an acquired form of disease (termed senile systemic amyloidosis). In recent years, advances in the diagnosis and treatment of cardiac amyloidosis include identification and validation of disease biomarkers, new imaging techniques, and consensus treatment guidelines. Elevations of B-type natriuretic peptide and cardiac troponins can identify cardiac amyloidosis with a high degree of precision and confer important prognostic information. Non-invasive cardiac imaging techniques, such as cardiac magnetic resonance imaging and echocardiography with strain quantification, afford the ability to diagnose cardiac amyloidosis most often without the need for a confirmatory heart biopsy. Treatment of heart failure resulting from cardiac amyloidosis differs in many respects from most other etiologies of cardiomyopathy. The mainstay of treatment involves volume control with diuretics, low dose β-adrenergic antagonists or amiodarone for dysrhythmia, and warfarin to prevent thromboembolism. Although widely held to have a dismal prognosis, modern treatments such as high-dose melphalan with stem cell transplantation (HDM/SCT) for AL disease achieve a complete hematologic response in nearly half of eligible patients and yield long-term survival. For patients with advanced AL cardiac amyloidosis, cardiac transplantation followed by HDM/SCT is also an option that has proven highly effective. For familial amyloid derived from variant TTR, liver transplantation is the one validated treatment; however, small molecule therapeutic agents now in clinical trials appear capable of slowing or halting TTR amyloid deposition.