Granular Sparkling Appearance Research Articles

P339 LIGHT–CHAIN CARDIAC AMYLOIDOSIS WITH FULMINANT EVOLUTION, A NOT–SO–RARE CONDITION: THE IMPORTANCE OF EARLY DIAGNOSIS

Abstract Introduction Amyloid AL results from misfolding of immunoglobulin light chain (kappa or lambda) secreted by abnormal plasma cells such as in multiple myeloma. It is a rare, multisystemic disease with an estimated annual incidence rate of 6 to 10 cases per million inhabitans in Western countries. The prognosis of this hematologic neoplasm is guided by the extent of cardiac involvement; if untreated, survival rate is less than 6 months; with early initiation of chemotherapy treatment, median survival can range from 4 to 10 years, except for high–risk cases. Case report: 58–year–old patient presented to emergency department in May 2022 with the first syncopal episode and sphincter release. The patient had no cardiovascular risk factors. Echocardiografy showed markedly hypertrophic left ventricle with hyper–reflective walls with a granular–sparkling appearance. Electromyography revealed sensory–motor polyneuropathy, early–stage autonomic neuropathy and bilateral carpal tunnel syndrome. Implantation of a loop recorder was performed to investigate the cause of syncope. In suspected amyloidosis, the patient underwent electrophoresis, which showed no monoclonal peaks, serum and urine kappa and lambda light chains were negative. Bone scintigraphy showed no osteotropic radiopharmaceutical uptake in the heart. Cardiac magnetic resonance imaging (MRI) revealed biventricular hypertrophic phenocopy (concentric hypertrophy) with diffuse edema–like tissue alterations. The patient was asymptomatic. In August 2022, hematologic evaluation revealed a monoclonal band for lambda light chains in repeated immunofixation and bone marrow biopsy showed 9–10% monoclonal lambda plasma cells. The patient was referred to a specialized center for amyloidosis, where a biopsy of peri–umbilical fat was performed to confirm the diagnosis and initiate therapy. In October 2022, due to recurrent syncope, advanced atrioventricular block and extreme bradycardia at loop recorder, a dual–chamber pacemaker was implanted. A few days after discharge, the patient suffered cardiac arrest at home due to electromechanical dissociation and died, only 5 months after the first symptom. Conclusion AL amyloidosis is an aggressive hematological neoplasm, with cardiac involvement. Early diagnosis is crucial for timely initiation of therapy, which is the only means available to increase patient survival. It is important to maintain a high level of awareness and diagnostic suspicion for this condition.

P351 FATAL RECURRING SYSTEMIC THROMBOEMBOLYSM IN A PATIENT WITH CARDIAC AL AMYLOIDOSIS WITHOUT EVIDENCE OF ATRIAL FIBRILLATION

Abstract Backgound: Cardiac amyloidosis is associated with an increased thromboembolic risk. While the need to anticoagulate patients in atrial fibrillation regardless of the CHA2DS2–VASc score is evident, it is not clear whether and which patients in sinus rhythm should be treated with anticoagulant drugs Case Presentation A 51–year–old man presented with repeated episodes of chest pain and exertional dyspnea. The ECG showed synus rhythm, left–axis deviation, 1st degree AV–block, left anterior hemiblock and no significant anomalies of ventricular repolarisation. Transthoracic echocardiography revealed markedly thickened left ventricular (IN) walls (maximum interventricular septum dimension 18 mm) with a granular–sparkling appearance of the myocardium, bi–atrial enlargement, preserved LV ejection fraction (EF 52%), restrictive mitral flow pattern with a very small A–wave, thickened interatrial septum and atrio– ventricular valves; circumferential pericardial effusion ( maximum 11mm). Laboratory tests showed an increase in troponin and NTproBNP levels and serum and urine immunoelectrophoresis showed a monoclonal component in zone kappa. A periumbilical fat biopsy was negative for amyloidosis so the patient underwent an endomyocardial biopsy which showed positive Congo red, and immunohistochemistry positive for kappa light chains and negative for transthyretin. A diagnosis of cardiac amyloidosis AL was then made and the patient was referred to the hematologist to perform specific therapy. One week after discharge he was hospitalized for acute pain in the lower limbs due to acute thrombosis of the left common femoral artery treated with Fogarty embolectomy. Discharged in therapy with low molecular weight heparin after a few days he was again symptomatic for pain in the lower limbs and went to the emergency room where he died of electromechanical dissociation. Conclusions Our case demonstrates that cardiac AL amyloidosis is associated with an increased thromboembolic risk, irrespective of the presence of atrial fibrillation, for the hematological disease itself and for the infiltration of the atrium by the amyloid substance. This suggests that in selected cases, with reduced A–wave amplitude and evidence of impaired atrial mechanics, empirical anticoagulation should be considered even in sinus rhythm.

517 RIGHT ATRIAL THROMBUS IN A PATIENT WITH CARDIAC AMYLOIDOSIS: A MULTIMODALITY IMAGING APPROACH

Abstract Case Presentation A 47-year-old man was referred to our outpatient clinic for dyspnea and chest pain. His past medical history was remarkable for an admission of acute congestive heart failure, occurred two weeks before presentation. On that occasion, the patient was discharged after a few days of diuretic therapy. Diagnostic Workup at presentation, the patient was symptomatic for dyspnea with signs of systemic congestion. The ECG showed sinus rhythm, inferolateral negative T waves and absent progression of R wave in precordial leads. Transthoracic echocardiography revealed markedly thickened left ventricular (LV) walls (maximum interventricular septum dimension 19 mm) with a granular-sparkling appearance of the myocardium, bi-atrial enlargement, preserved LV ejection fraction, restrictive mitral flow pattern thickened interatrial septum and atrio-ventricular valves. No significant valvular regurgitations were detected. Global LV longitudinal strain was significantly reduced (-9.4%), with relative apical sparing. Given the high suspicion for infiltrative disease we performed further investigations. The cardiac computed tomography (CCT) excluded significant coronary artery disease, but it raised the suspicion of a thrombus at the level of the right atrial appendage, that was confirmed by a transesophageal echocardiography showing a mobile round mass of 14×12 mm. Finally, tissue characterization by cardiac magnetic resonance exhibit a diffuse myocardial delayed enhancement, with a dark blood pool and, an increase in extracellular volume and T1 mapping values (1266.3 ms). Laboratory tests showed increased levels of creatinine, BNP and, lambda light chains. Bone scintigraphy imaging didn't identify any uptake of radiotracers at myocardial level. These findings were suggestive for cardiac light-chain (AL) amyloidosis. Accordingly, a treatment with warfarin, beta-blockers, steroid, and diuretics was initiated. Conclusions cardiac amyloidosis is an infiltrative disease characterized by the deposition of aggregates of amyloid fibrils in the myocardium. Multimodality imaging is pivotal to determine the diagnosis, assess the potential complications, and stratify the patients’ prognosis. Our case demonstrates that cardiac AL amyloidosis is associated with an increased thromboembolic risk, irrespective of the presence of atrial fibrillation. Moreover, although the left atrial appendage is most frequently the site of thrombus formation, it is advised to look for them also in uncommon sites as the right atrial appendage.

P310 CARDIAC AMYLOIDOSIS: INITIAL MONOCENTRIC EXPERIENCE

Abstract Cardiac amyloidosis is a group of diseases characterized by the accumulation in the interstitial space of amorphous material consisting of amyloid fibrils and, until recently, considered rare, with poor therapeutic prospects and burdened by a poor prognosis. However, both for amyloidosis from immunoglobulin light chains (AL) and for transthyretin amyloidosis in its wild type and mutated forms, there has been a significant increase in diagnostic capabilities. The aim of this work is to show the characteristics found in our population affected by cardiac amyloidosis. Materials and Methods We enrolled 18 patients observed over 12 months. The mean age was 63 ± 5, 14 patients were male. 8 patients in NYHA Class I – II, 10 patients in NYHA Class II – III. On the ECG in 88% of cases low QRS voltages in the peripheral leads. Among the conduction disturbances: 1st degree AV block in 45%, EAS in 33%, BBSn in 17%, occurrence of isolated BEV and BESV in 90%; 1 patient presented with AF. Defibrillator was implanted in 3 patients for detection of TVS and TNnS. In the whole population, the echocardiogram showed concentric parietal hypertrophy with a granular sparkling appearance; the mean FE was 55 ± 3%, the diastolic filling pattern was altered in type I in 42%, type II in 33% and type III in 25% of patients, respectively. In 92% of cases the left atrium was dilated. In 87% of cases there was an involvement of the valves in particular in 64% of cases we found calcifications of the aortic valve and in 66% mitral insufficiency. In 42% of patients there was an increase in the thickness of the atrial septum as well as the free wall of the right ventricle. Finally, signs of non–buffering pericardial effusion were found in 33% of patients. Results In our study population, 15 patients had multiple myeloma and presented with cardiac AL–type amyloidosis; among these 3 also presented renal involvement. In 3 patients, on the other hand, after positive bone scan and genetic screening, we diagnosed cardiac amyloidosis due to transthyretin mutation for which therapy with Tafamidis was undertaken. 3 patients died. Conclusions Our population presented echographic and echocardiographic characteristics comparable to those reported in the literature.

P319 SOMETHING MORE OF SIMPLE CARDIAC CONDUCTION DISORDERS

Abstract Background Cardiac amyloidosis (CA) is an infiltrative disease caused by extracellular deposition of amyloid fibrils. Possible cardiac manifestations include heart failure with preserved ejection fraction (EF), aortic valve stenosis, microvascular coronary artery disease, atrial fibrillation (AF), ventricular arrhythmias, and cardiac conduction disorders (CCD). We report a case of advanced CCD in a patient first diagnosed with wild–type transthyretin amyloidosis (ATTRwt). Case Report An 88–year–old man went to Emergency Room for chest pain with minimal elevation of troponin I and increase in NTproBNP. The patient reported a recent syncope with ribs fractures. The medical history showed hypertension, paroxysmal AF, carotid atherosclerosis, vascular encephalopathy and prostate cancer. Troponin I monitoring showed plateau values and there were no clinical signs of heart failure. ECG showed regular sinus rhythm with marked first degree atrioventricular block, right bundle branch block and left anterior fascicular block (Fig. 1A). Cardiac telemetry recorded brief phases of atrioventricular dissociation (AVD). Transthoracic echocardiography showed severe left ventricular concentric hypertrophy (LVCH) with granular–sparkling appearance and preserved EF, reduced global longitudinal strain with apical sparing (Fig. 1B), mitral–aortic valve degeneration and dilation of the ascending aorta. Given the advanced CCD with AVD and the recent syncope, the patient underwent a dual–chamber pacemaker implantation. In consideration of the echocardiographic suspicion of CA, following Gillmore’s diagnostic algorithm (GDA), serum electrophoresis and assay of serum free light chains were performed and resulted normal, while 99mTc–DPD bone scintigraphy was positive for significant radiotracer cardiac uptake (Perugini grade 3) (Fig. 1C). Based on this result, we carried out the search for transthyretin gene mutations which resulted negative, and therefore the diagnosis of ATTRwt was made. Discussion Advanced CCD in patients with transthyretin CA are present in about 9.5% of cases at the time of diagnosis, especially in older patients. It is therefore essential, in case of concomitant LVCH, to suspect the presence of CA as the cause of CCD by searching for the disease red flags and following the GDA to non–invasively confirm or exclude the diagnosis of CA. A correct and timely diagnosis of CA makes it possible to treat the disease and its complications, improving the prognosis.

325 Dealing with cardiac amyloidosis diagnosis: keep calm and use the magnifying glasses!

Abstract Methods and results Case report— male, 71 years old. Past medical history—arterial hypertension, dyslipidemia, tobacco abuse. COPD on nocturnal CPAP therapy. Rheumatic polymyalgia on steroid therapy. Previous unprovoked deep vein thrombosis on anticoagulation with rivaroxaban. Bilateral carpal tunnel surgeries 8 years ago. Spontaneous left biceps tendon rupture 4 year ago. IgA kappa monoclonal gammopathy of undetermined significance (MGUS). Mild interventricular septum (IVS) hypertrophy on echocardiography since 2018. In 2019 IVS was 18 mm with granular sparkling appearance. In February 2020 he was hospitalized for initial heart failure and COPD exacerbation. In 2021 he developed worsening dyspnoea. He underwent cardiological evaluation in a spoke hospital and a cardiac magnetic resonance (CMR) suggested infiltrative cardiomyopathy. Bone scintigraphy showed moderate cardiac uptake (Perugini Score 2). Following haematological evaluation, fat pad biopsy was performed, and amyloid was detected on Congo red staining. Classification of the amyloid fibril protein was not performed. Bone marrow biopsy, even though of suboptimal quality, was negative for amyloid and for plasma cellular infiltration. Bone marrow aspirate showed 11% of plasma cells and multiple myeloma was therefore hypothesized. Recent medical history—he was evaluated in our Cardiac Amyloid Outpatient Clinic in May 2021. He was symptomatic for dyspnoea (NYHA class III) and exercise intolerance, diffuse osteo-muscolar pain, and extremities paresthesia. His blood pressure was on the low side of normality with necessity of anti-hypertensive therapy downgrading. Signs and symptoms of hematological disease were not present. We required to analyse the fat pad specimen in order to perform amyloid fibril protein typing; with immunoelectron microscopy, transthyretin (TTR) was identified as the amyloid fibrils precursor (no light chains could be identified). We considered performing endomyocardial biopsy to exclude the coexistence of ATTR amyloidosis and light chains (AL) amyloidosis in the heart but, given the history, clinical picture, and fat pad biopsy results, we felt that cardiac ATTR was the most probable diagnosis and we decided to proceed with a close cardiological and haematological follow-up. TTR genetic testing is ongoing. Conclusions ATTR cardiac amyloidosis is an emerging cause of heart failure, especially with preserved ejection fraction, in the older population. However, these patients frequently present with dysproteinemias and bone marrow abnormalities, up to multiple myeloma, raising the issue of differential diagnosis between ATTR and AL amyloidosis. According to the latest European Consensus Document, in the presence of cardiac uptake at bone scintigraphy (Grades 1–3) and positive haematologic tests, histological confirmation (usually cardiac) is necessary to subtype amyloid infiltration. In our case, the patient had positive Congo Red-stained fat pad biopsy, but the typing of the amyloid deposition was not performed. After referral to a Center with a Cardiac Amyloid Outpatient Clinic with a specialized Pathology Unit, we could further proceed with diagnostic workup and identify the amyloid deposition as ATTR; of note, fat pad biopsy is positive in just 15–25% of ATTR amyloidosis. Moreover, close collaboration with Hematology was necessary to assess the risk of AL amyloidosis and to provide a close and targeted follow-up. Endomyocardial biopsy was not performed after consideration of the various elements suggestive for ATTR cardiac amyloidosis, but the patient will be evaluated periodically and closely to potentially reassess this decision.

Reversible myocardial oedema due to acute myocardial infarction as differential diagnosis of cardiac transthyretin amyloidosis

Using bone‐avid radiotracers, cardiac transthyretin (TTR) amyloidosis can be diagnosed by scintigraphy, thus obviating endomyocardial biopsy. Radiotracer accumulation, however, may also be due to other causes. A 68‐year‐old male with acute myocardial infarction underwent recanalization of the left anterior descending coronary artery (LAD). Postinterventionally, transthoracic echocardiography showed hypokinesia of the septum and anterior wall and a thickened myocardium with granular sparkling appearance. Cardiac amyloidosis was suspected. A 99mTc‐3,3‐diphosphono‐1,2‐propanodicarboxylic acid whole‐body scan 4 days after LAD recanalization showed Perugini 2 myocardial tracer uptake. Monoclonal gammopathy was excluded, and cardiac TTR amyloidosis was diagnosed. Three months later, 99m‐Tc‐hydroxydiphosphate scan showed no myocardial tracer uptake. Cardiac magnetic resonance imaging revealed late gadolinium enhancement within the LAD supply area. No mutation of the TTR gene was found. Suspicion of amyloidosis should consider not only echocardiography but also history and clinical findings. Myocardial oedema due to reperfusion should be acknowledged as a differential diagnosis for cardiac uptake of bone‐avid radiotracers.

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

BackgroundThe disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical.MethodsWe retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center.ResultsEight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%).ConclusionsThis study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.

Apical Sparing of Longitudinal Strain, Left Ventricular Rotational Abnormalities, and Short-Axis Dysfunctionin Primary Hyperoxaluria Type 1

A 24-year-old woman with end-stage renal failure because of primary hyperoxaluria type 1 was evaluated in our hospital for systemic calcium oxalate deposition in the course of long-term (5 years) hemodialysis therapy. Diagnosis of primary hyperoxaluria type 1, a hereditary cause of calcium oxalate kidney stones or progressive nephrocalcinosis that frequently results in end-stage renal failure,1 was made by liver biopsy (reduced alanine:glyoxylate aminotransferase activity, 3.0 µmol/h per milligram protein; normal, 19.1–47.9) and by genetic testing (homozygosity for the c.302 T>C, AGXT mutation). Her plasma oxalate level on regular hemodialysis (3× per week over 4 hours) was increased (86 µmol/L predialysis; normal, <10 µmol/L). Transthoracic echocardiography revealed increased wall thickness of the left ventricle (LV; Figure 1). The LV was mildly dilated and showed a decreased systolic function. Flow across the mitral valve demonstrated a restrictive filling pattern. Moreover, the myocardium had a characteristic echo-dense granular sparkling appearance (Movie in the online-only Data Supplement).2 Both atria were enlarged. Moderate tricuspid regurgitation was present. A right ventricle systolic pressure of 62 …

Periorbital Ecchymoses Are Not Pathognomonic of the Light-chain Type of Amyloidosis

CASE REPORT A 52-year-old man presented with a progressive 16month course of severe sensorimotor polyneuropathy. He had no personal or familial medical past history. Clinical manifestations appeared in July 2003 and were characterized by decreased sensation and painful paraesthesia of the upper extremities, followed 4 months later by distal weakness. Then, decreased sensation, painful paraesthesia and distal weakness of the lower limbs progressively appeared. Alternating diarrhoea and constipation, Raynaud’s syndrome and erectile dysfunction were noted at the same time. The patient also complained of effort dyspnoea and orthopnoea. Electromyography demonstrated a severe axonal sensorimotor polyneuropathy involving all 4 limbs. Investigations revealed a normal blood count and serum glucose, creatinine, and urea, electrolytes and liver function test. There were no inflammatory biological markers. Classical causes of axonal polyneuropathy, such as alcoholism, vitamin deficiency, diabetes melli tus, dysthyroidea and auto-immune diseases, were ruled out. The suspected dysautonomia was confirmed by an abnormal heart-rate variability on electrophysiological tests. Echocardiography showed thickened ventricular walls with a granular sparkling appearance and impaired diastolic dysfunction. The patient developed periorbital and scleral ecchymoses after vomiting (Fig. 1). Since periorbital ecchymoses are classically considered as pathognomonic of AL amyloidosis, we performed a salivary gland biopsy and a sural nerve biopsy. Amyloid deposits were observed in both figures, but immunofluorescence with anti-light-chain (lambda or kappa) antibodies did not reveal any immunoreactivity. There was no evidence of monoclonal gammopathy in spite of an exhaustive work-up comprising blood and urinary immunoelectrophoresis, nephelometric assay of light chain in serum and an osteomedullar biopsy. Since the AL type of amyloidosis was not confirmed, a molecular analysis of the TTR gene was performed and revealed a heterozygous Ser77Tyr mutation, resulting in a diagnosis of familial TTR type amyloid polyneuropathy. Immunohistochemistry confirmed the transthyretin nature of the amyloid deposits (Fig. 2).

Echocardiographic findings in systemic amyloidosis: Spectrum of cardiac involvement and relation to survival

One hundred thirty-two patients with biopsy-proven systemic amyloidosis underwent echocardiographic examination to define the spectrum of cardiac involvement. Echocardiographic abnormalities were then correlated with clinical variables and survival at follow-up. Patients were subgrouped by left ventricular wall thickness: Group I, mean wall thickness 12 mm or less; Group II, mean wall thickness greater than 12 mm but less than 15 mm; Group III, mean wall thickness 15 mm or greater; or Group IV, atypical features such as wall motion abnormalities or left ventricular dilation. Patients with greater wall thickness had a higher frequency of associated echocardiographic abnormalities such as left atrial enlargement or granular sparkling appearance on two-dimensional examination and, more commonly, reduced systolic function. The occurrence of clinical congestive heart failure was strongly correlated with greater wall thickness and multiple other echocardiographic abnormalities. Survival was negatively influenced both by greater wall thickness and reduced systolic function. The median survival of the entire group was 1.1 years. Echocardiographic examination is an important tool for establishing the presence of cardiac amyloid involvement and may be useful in estimating prognosis in such patients.