Early Diagnosis Of Cardiac Amyloidosis Research Articles

Diagnosis of cardiac amyloidosis with the use of modern ultrasound techniques

Amyloidosis is a systemic disease caused by accumulation of insoluble amyloid proteins in the tissues. Cardiac amyloidosis (CA) lead to a severe heart failure, which is often therapy resistant. The severity of heart failure does not correspond to the degree of decrease in systolic function of the left ventricle, since diastolic function is more impairing. Early diagnosis of cardiac amyloidosis is important due to the presence of treatment regimens for this disease nowadays. The “gold standard” for cardiac amyloidosis diagnosis is myocardial biopsy, but non-invasive diagnostic methods are also of great importance. The aim of the article is a review of the ultrasound signs of cardiac amyloidosis, including the use of modern technologies, which helps to suspect CA to provide a further examination.

Novel electrocardiographic criteria may render possible the more accurate recognition of cardiac amyloidosis.

The early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose. We tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I<0.55mV (I<0.55); QRS amplitude in lead aVR<0.5mV (aVR<0.5); average QRS amplitude of leads I+aVR<0.575mV [(I+aVR)<0.575]; average QRS amplitude of leads I+aVR/average QRS amplitude of leads V1-4<0.375 [(I+aVR)/(V1-4)<0.375]; average QRS amplitude of leads I+aVR/longest intrinsicoid deflection in leads I,aVL,V1-6<0.0115 [(I+aVR)/I,aVL,V1-6ID<0.0115]. The I<0.55, aVR<0.5, (I+aVR)<0.575, (I+aVR)/(V1-4)<0.375, (I+aVR)/I,aVL,V1-6ID<0.0115 test accuracy (TA) were 81%, 84.8%, 82.3%, 84.8%, and 83.3%, respectively; the sensitivity (SE): 76.5%, 82.4%, 85.3%, 82.4%, and 76.9%; specificity (SP): 84.4%, 86.7%, 80%, 86.7%, and 87.5%; positive predictive values (PPV): 78.8%, 82.4%, 76.3%, 82.4%, and 80%; negative predictive values (NPV): 82.6%, 86.7%, 87.8%, 86.7%, and 85.4%; area under curve (AUC) values: 0.8922, 0.8794, 09016, 0.8824, and 0.8462 were respectively. These parameters of the novel ECG criteria were at least as good as those reported by other authors in the literature of the qualitative (TA: 67%, SE: 80%, SP: 34%, PPV: 75%, NPV: 42%, AUC: 0.57) and quantitative apical sparing (TA: 64-80%, SE: 66-81.3%, SP: 55-78.3%, PPV: 33-83.9%, NPV: 41-75%, AUC: 0.62-0.68) and left ventricular ejection fraction/global longitudinal strain >4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%). The novel ECG criteria [mostly the aVR<0.5, (I+aVR)/(V1-4)<0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand-alone criteria to diagnose CA in the future.

Prevalence of cardiac amyloidosis in patients undergoing carpal tunnel release with amyloid deposition in removed tenosynovium

Abstract Background Carpal tunnel syndrome (CTS) is an early symptom and important clinical indicator for the diagnosis of cardiac amyloidosis. Amyloid deposition in removed tenosynovium during carpal tunnel release (CTR) is often confirmed; however, the prevalence of concomitant cardiac amyloidosis is not yet understood. Purpose This study aimed to evaluate the prevalence of amyloid deposition in removed tenosynovium in patients who underwent CTR and to clarify the prevalence of concomitant cardiac amyloidosis in patients who had amyloid deposition in removed tenosynovium. Methods Overall, 669 patients who underwent CTR were prospectively examined and evaluated for amyloid deposition after tenosynovium removal. Invitation and proposal letters for cardiac screening were sent to patients with amyloid deposition. Electrocardiography, echocardiography, and biomarkers were evaluated to assess the likelihood of cardiac amyloidosis. Results Amyloid deposition was observed in 261 (39%) patients, who were significantly older and predominantly male (p&amp;lt;0.05). Among them, 111 patients (mean age; 70.8 ± 7.3 years old; men: 55%) agreed to cardiac screening. 99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy was performed in 12 patients who met the following criteria: 1) interventricular septum diameter (IVSd) ≥14 mm or 2) 12 mm ≤ IVSd &amp;lt;14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT; &amp;gt;0.014 ng/mL). Six patients (50%) had positive findings on 99mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin cardiac amyloidosis with Mayo prognostic stage I. The prevalence of concomitant cardiac amyloidosis was observed in 6/111 (5.4%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. Conclusion Amyloid deposition in removed tenosynovium was frequently observed in elderly men with CTS. Cardiac screening may be useful for the early diagnosis of cardiac amyloidosis in patients undergoing CTR with amyloid deposition. This knowledge should be shared with orthopedic surgeons and cardiologists for the early diagnosis of cardiac amyloidosis.Flowchart of participant selectionGraphical Abstract

Diagnostics of cardiac amyloidosis

The early diagnosis of cardiac amyloidosis is decisive for the success of treatment of affected persons. The thorough clinical investigation of the patient should be followed by appropriate diagnostics using modern procedures. The main symptoms are dyspnea, loss of performance and edema and in later stages cardiac arrhythmias in the form of atrioventricular conduction disturbances and atrial fibrillation but ventricular arrhythmias occur more rarely. During heart failure due to cardiac amyloidosis an increase of cardiac enzymes frequently occurs (e.g., creatine kinase, troponin, N‑terminal pro-brain natriuretic peptide), which can be included in the risk stratification and treatment monitoring, taking certain limitations into consideration. The investigation of light chains in serum and/or urine should be carried out immediately, as soon as there is a clinical and echocardiographic suspicion of cardiac amyloidosis. Subsequently, either cardiac magnetic resonance imaging (MRI) or bone scintigraphy should be carried out, depending on the locally available options. Depending on the results of these two imaging procedures, a decision must be made as to whether further diagnostic steps (e.g., endomyocardial biopsy) are necessary. In the last decade bone scintigraphy has proven to be a blessing for the diagnostics of cardiac amyloidosis but many partial aspects and limitations necessitate special and careful consideration. A Perugini score of 2 or 3 is initially "indicative" of cardiac amyloidosis but not yet "confirmative" for a specific subtype. Only after an additional negative result of the light chain determination, can the diagnosis of ATTR amyloidosis be noninvasively made. Cardiac amyloidosis shows a particularly characteristic contrast enhancement in cardiac MRI, which mostly begins in the inner (subendocardial) layers of the basal left ventricular (LV) wall and frequently appears to be circular in the cross-sectional view of the left ventricle. Supplementary T1 and extracellular volume fraction mapping results, which are shown as color-coded maps, enable the rapid and elegant assessment of the myocardial structure and the extent of amyloid deposition. An additional investigation of the TTR gene is recommended in the case of ATTR amyloidosis for a differentiation between hereditary and acquired ATTR, as from this, further therapeutic consequences can be derived.

Detection and Diagnosis of Cardiac Amyloidosis in Egypt.

Cardiac amyloidosis is a life-threatening disease that occurs when amyloid proteins, most commonly immunoglobulin light chain or transthyretin, mutate or become unstable, misfold, deposit as amyloid fibrils, and accumulate in the myocardium. Early diagnosis of cardiac amyloidosis is hindered by insufficient awareness, specifically regarding clinical red flags and diagnostic pathways. Cardiac amyloidosis diagnosis comprises two important phases, clinical suspicion (phase one) followed by definitive diagnosis (phase two). Each phase is associated with specific clinical techniques. For example, clinical features, electrocardiography, echocardiography, and cardiac magnetic resonance imaging serve to raise suspicion of cardiac amyloidosis and facilitate early diagnosis, whereas laboratory tests (i.e., blood or urine electrophoresis with immunofixation), biopsy, scintigraphy-based nuclear imaging, and genetic testing provide a definitive diagnosis of cardiac amyloidosis. In Egypt, both the lack of cardiac amyloidosis awareness amongst healthcare providers and the unavailability of clinical expertise for the use of diagnostic techniques must be overcome to improve the prognosis of cardiac amyloidosis in the region. Previously published diagnostic algorithms for cardiac amyloidosis have amalgamated techniques that can raise clinical suspicions of cardiac amyloidosis with those that definitively diagnose cardiac amyloidosis. Though such algorithms have been successful in developed countries, diagnostic tools like echocardiography, scintigraphy, and cardiac magnetic resonance imaging are not ubiquitously available across Egyptian facilities. This review presents the current state of knowledge regarding cardiac amyloidosis in Egypt and outlines a new diagnostic algorithm which leverages regional nuclear imaging expertise. Importantly, the proposed diagnostic algorithm guides accurate amyloid-typing to mitigate misdiagnosis and erroneous treatment selection and improve the cardiac amyloidosis diagnostic accuracy in Egypt.

Abstract 15382: Geriatric HFpEF: When It Isn’t Hypertensive Heart Disease

Introduction: Transthyretin amyloid cardiomyopathy (ATTR) is thought to be a rare cause of HF, but recent studies showed this is the cause of 30% of HFpEF patients older than 75. With new treatments for amyloidosis, timely diagnosis has become critical. Case: A 78-female with HFpEF, HTN, and diabetes followed for progressive functional decline and hospitalizations for HFpEF exacerbations. EKG at baseline showed LBBB with normal QRS voltages. Serial echocardiogram (echo) showed an ejection fraction (EF) of 60-70%, mild LVH, and moderate TR with RVSP &gt;50 mmHg. Latest echo showed progressive LA enlargement, MR, a new small pericardial effusion, and EF 50%. Regadenoson nuclear scan showed normal perfusion with preserved LVEF. Despite adequate control of her HTN, dyspnea continued to worsen. Because of this, the diagnosis of Cardiac amyloidosis was considered. Further review revealed a history of Carpal Tunnel Syndrome (CTS) and speckled pattern within the ventricular wall on echo. A technetium pyrophosphate scintigraphy ( 99m Tc-PYP) confirmed ATTR with grade three uptake, AL amyloid was ruled out with normal SPEP/UPEP, and she was started on Tafamidis. Discussion: Cardiac amyloidosis should be considered in HFpEF patients with functional decline despite medical optimization. It can mimic LVH caused by HTN on echo and easily dismissed in patients with traditional risk factors, but presence of CTS or lumbar spinal stenosis can be supportive. Traditionally ATTR is associated with low-voltage EKG, however this patient presented with normal QRS voltages for years, making the diagnosis more elusive. Conclusion: Advances in noninvasive imaging and treatments allow for early diagnosis of cardiac amyloidosis, reducing morbidity and mortality. Diagnosis is often delayed or missed, as features could be subtle and mimic other more common cardiac disease. Screening&amp;nbsp; 99m Tc-PYP for elderly patients with HFpEF could translate to improved outcomes

Hypertension is associated with more advanced heart failure in african americans with suspected cardiac amyloidosis

Abstract Background Prior studies have shown worse clinical outcomes for African Americans with transthyretin and light chain cardiac amyloidosis as compared to Caucasians. Hypertensive heart disease is common among African Americans, and a known echocardiographic mimic of cardiac amyloidosis. The association between hypertension and heart failure severity in patients with suspected cardiac amyloidosis has not been well characterized. Purpose We sought to identify phenotypic differences between African American and Caucasian patients with suspected cardiac amyloidosis with and without hypertension. Methods We retrospectively identified consecutive patients who underwent cardiac biopsy for evaluation of cardiac amyloidosis at our institution between 2000–2018. Clinical and demographic data were obtained from the medical record. Electrocardiograms and echocardiograms performed at the time of cardiac biopsy were interpreted by study personnel. Results Among 230 patients with suspected cardiac amyloidosis, 144 (58%) had a prior diagnosis of hypertension. Hypertension was more common among African Americans (71 of 91, 78%) than among Caucasians (73 of 139, 52%). Among African Americans with suspected cardiac amyloidosis, those with hypertension had higher left ventricular mass index (156 versus 119 g/m2), lower left ventricular ejection fraction (47% versus 56%), worse global longitudinal strain (−9.0% versus −11.7%), and higher creatine (1.95 versus 1.43 mg/dL) than those without hypertension (p&amp;lt;0.05 for all). There were no differences in these parameters among Caucasians with and without hypertension. Conclusions Among African Americans with suspected cardiac amyloidosis, those with hypertension had worse systolic function and more advanced heart failure than those without hypertension. Targeted screening and/or surveillance strategies are needed to improve early diagnosis of cardiac amyloidosis in African American patients with hypertension. Funding Acknowledgement Type of funding sources: None.

Advanced Imaging in Cardiac Amyloidosis.

This review serves as a synopsis of multimodality imaging in cardiac amyloidosis (CA), which is a disease characterized by deposition of misfolded protein fragments in the heart. It emphasizes and summarizes the diagnostic possibilities and their prognostic values. In general, echocardiography is the first diagnostic tool in patients with an identified systemic disease or unclear left ventricular hypertrophy. Several echocardiographic parameters will raise suspicion and lead to further testing. Cardiac magnetic resonance and scintigraphy with bone avid radiotracers are crucial for diagnosis of CA and even enable a distinction between different subtypes. The subject is illuminated with established guidelines and innovative recent publications to further improve early diagnosis of cardiac amyloidosis in light of current treatment options.

Diagnostic Work-Up of Cardiac Amyloidosis Using Cardiovascular Imaging: Current Standards and Practical Algorithms.

Among non-ischemic cardiomyopathies, cardiac amyloidosis is one of the most common, being caused by extracellular depositions of amyloid fibrils in the myocardium. Two main forms of cardiac amyloidosis are known so far, including 1) light-chain (AL) amyloidosis caused by monoclonal production of light-chains, and 2) transthyretin (ATTR) amyloidosis, caused by dissociation of the transthyretin tetramer into monomers. Both AL and ATTR amyloidosis are progressive diseases with median survival from diagnosis of less than 6 months and 3 to 5 years, respectively, if untreated. In this regard, death occurs in most patients due to cardiac causes, mainly congestive heart failure, which can be prevented due to the presence of effective, life-saving treatment regimens. Therefore, early diagnosis of cardiac amyloidosis is crucial more than ever. However, diagnosis of cardiac amyloidosis may be challenging due to variable clinical manifestations and the perceived rarity of the disease. In this regard, clinical and laboratory reg flags are available, which may help clinicians to raise suspicion of cardiac amyloidosis. In addition, advances in cardiovascular imaging have already revealed a higher prevalence of cardiac amyloidosis in specific populations, so that the diagnosis especially of ATTR amyloidosis has experienced a >30-fold increase during the past ten years. The goal of our review article is to summarize these findings and provide a practical approach for clinicians on how to use cardiovascular imaging techniques, such as echocardiography, cardiac magnetic resonance, bone scintigraphy and, if required, organ biopsy within predefined diagnostic algorithms for the diagnostic work-up of patients with suspected cardiac amyloidosis. In addition, two clinical cases and practical tips are provided in this context.

Aortic Valve Stenosis and Cardiac Amyloidosis: A Misleading Association

The association between aortic stenosis (AS) and cardiac amyloidosis (CA) is more frequent than expected. Albeit rare, CA, particularly the transthyretin (ATTR) form, is commonly found in elderly people. ATTR-CA is also the most prevalent form in patients with AS. These conditions share pathophysiological, clinical and imaging findings, making the diagnostic process very challenging. To date, a multiparametric evaluation is suggested in order to detect patients with both AS and CA and choose the best therapeutic option. Given the accuracy of modern non-invasive techniques (i.e., bone scintigraphy), early diagnosis of CA is possible. Flow-charts with the main CA findings which may help clinicians in the diagnostic process have been proposed. The prognostic impact of the combination of AS and CA is not fully known; however, new available specific treatments of ATTR-CA have changed the natural history of the disease and have some impact on the decision-making process for the management of AS. Hence the relevance of detecting these two conditions when simultaneously present. The specific features helping the detection of AS-CA association are discussed in this review, focusing on the shared pathophysiological characteristics and the common clinical and imaging hallmarks.

Cardiac amyloidosis‐A review of current literature for the practicing physician

The amyloidoses are a family of diseases in which misfolded precursor proteins aggregate to form amyloid and deposit in body tissues. A very serious yet underrecognized form of this disease is cardiac amyloidosis, in which amyloid deposits into the extracellular space of the myocardium, resulting in thickening and stiffening of ventricular walls with resultant heart failure and conductive dysfunction. This review provides a discussion of the pathogenesis and clinical presentation of cardiac amyloidosis subtypes, as well as an up‐to‐date approach to diagnosis and treatment. Significant progress has been made in recent years regarding diagnosis and treatment of this condition, but prognosis remains heavily reliant on early detection of the disease. Two types of precursor protein are responsible for most cardiac amyloidosis cases: transthyretin amyloid, and immunoglobulin‐derived light chain amyloid. An early diagnosis of cardiac amyloidosis can allow for novel treatment modalities to be initiated with the potential to improve prognosis.

A simple echocardiographic score to rule out cardiac amyloidosis.

Early diagnosis of cardiac amyloidosis (CA) is warranted to initiate specific treatment and improve outcome. The amyloid light chain (AL) and inferior wall thickness (IWT) scores have been proposed to assess patients referred by haematologists or with unexplained left ventricular (LV) hypertrophy, respectively. These scores are composed of 4 or 5 variables, respectively, including strain data. Based on 2 variables common to the AL and IWT scores, we defined a simple score named AMYLoidosis Index (AMYLI) as the product of relative wall thickness (RWT) and E/e' ratio, and assessed its diagnostic performance. In the original cohort (n=251), CA was ultimately diagnosed in 111 patients (44%). The 2.22 value was selected as rule-out cut-off (negative likelihood ratio [LR-] 0.0). In the haematology subset, AL CA was diagnosed in 32 patients (48%), with 2.36 as rule-out cut-off (LR- 0.0). In the hypertrophy subset, ATTR CA was diagnosed in 79 patients (43%), with 2.22 as the best rule-out cut-off (LR- 0.0). In the validation cohort (n=691), the same cut-offs proved effective: indeed, there were no patients with CA in the whole population or in the haematology or hypertrophy subsets scoring<2.22, <2.36 or<2.22, respectively. The AMYLI score (RWT*E/e') may have a role as an initial screening tool for CA. A<2.22 value excludes the diagnosis in patients undergoing a diagnostic screening for CA, while a<2.36 and a<2.22 value may be better considered in the subsets with suspected cardiac AL amyloidosis or unexplained hypertrophy, respectively.

Imaging Techniques as an Aid in the Early Detection of Cardiac Amyloidosis.

The idea that performing a proper succession of imaging tests and techniques allows an accurate and early diagnosis of cardiac amyloidosis, avoiding the need to perform the myocardial biopsy, is becoming increasingly popular. Furthermore, being imaging techniques non-invasive, it is possible to perform the follow-up of the pathology through repeated image acquisitions. In the present review, the various innovative imaging methodologies are presented, and it is discussed how they have been applied for early diagnosis of cardiac amyloidosis (CA), also to distinguish the two most frequent subtypes in CA: immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR); this allows to perform the therapy in a targeted and rapid manner.

Trends in Diagnostic Imaging of Cardiac Amyloidosis: Emerging Knowledge and Concepts.

Cardiac amyloidosis (CA) has long been recognized as a rare disease. However, recent advances in cardiac imaging have led to increased identification of hidden CA in patients diagnosed with heart failure. This shift suggests that the actual incidence of CA is underestimated. The prognosis of CA is generally poor, especially in patients with advanced heart failure. However, recent developments in therapeutic interventions have improved the survival of patients with CA. An early diagnosis and interventions involving effective therapies are essential contributors to improved prognoses. Recent noninvasive diagnostic imaging modalities such as echocardiography, cardiac MRI, and nuclear imaging have facilitated the precise and early diagnosis of CA and enabled the initiation of appropriate management. The authors present an updated review of the clinical features of CA, including a discussion of current trends in noninvasive diagnostic imaging. ©RSNA, 2020.

Trigger Finger and Amyloid Cardiomyopathy, Usual Suspect; Amyloid Deposition

Objectives: The aim of this study was to investigate the amyloid deposition in patients with trigger finger disease, to analyze the factors affecting amyloid deposition. In addition, we aimed to research the presence of cardiac amyloidosis in patients with amyloid deposition in flexor pulleys. Methods: Consecutive 68 patients with trigger finger treated by open release between September 2018 and November 2019 in two different hospitals were included in this study. Idiopathic trigger fingers were solely included. Patients with systemic rheumatoid diseases, chronic renal failure under hemodialysis, gout, tuberculous synovitis and previously diagnosed systemic amyloidosis including familial amyloid poly- neuropathy or multiple myeloma, pregnant patients, patients who were previously had steroid injected injections were excluded. Demographic data, other concomitant diseases and previous carpal tunnel surgeries were recorded. Immunoperoxidase and immunofluorescence methods were used to determine the amyloid presence and subtype in pathological A1 pulley specimens. Patients with amyloid deposition in biopsy specimen were further evaluated for cardiac involvement of amyloidosis. Results: The study population consisted of 18 men and 50 women with a mean age of 57,6 ± 12,2 years. Of 68 patients with trigger finger, 6 (8,8%) showed amyloid deposition in the tenosynovial tissue; and all amyloid deposits were specifically immunolabeled only with the anti-TTR antibody. No evidence of cardiac amyloidosis is found in patients with localized amyloid deposition. Conclusion: Hand surgeons should be aware of the association trigger finger and amyloidosis and consider biopsy of tenosynovial tissue particularly in patients with older age, DM, prior carpal tunnel release surgery and multi-finger involvement. Tenosynovial biopsy is a low-risk procedure that may guide to cardiologic examination of patients with positive biopsy and it will contribute to early diagnosis of cardiac amyloidosis.

El volumen extracelular detecta la amiloidosis cardiaca y está correlacionado con el deterioro neurológico en la amiloidosis familiar relacionada con la transtiretina

Introduction and objectivesCardiac involvement determines prognosis and treatment options in transthyretin-familial amyloidosis. Cardiac magnetic resonance T1 mapping techniques are useful to assess myocardial extracellular volume. This study hypothesized that myocardial extracellular volume allows identification of amyloidotic cardiomyopathy and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. MethodsA total of 31 transthyretin-familial amyloidosis patients (19 mean age, 49 ± 12 years; 26 with the Val30Met mutation) underwent a T1 mapping cardiac magnetic resonance study and a neurological evaluation with Neuropathy Impairment Score of the Lower Limb score, Norfolk Quality of Life questionnaire, and Karnofsky index. ResultsFive patients had cardiac amyloidosis (all confirmed by 99mTc-DPD scintigraphy). Mean extracellular volume was increased in patients with cardiac amyloidosis (0.490 ± 0.131 vs 0.289 ± 0.035; P = .026). Extracellular volume correlated with age (R = 0.467; P = .008), N-terminal pro-B-type natriuretic peptide (RS = 0.846; P < .001), maximum wall thickness (R = 0.621; P < .001), left ventricular mass index (R = 0.685; P < .001), left ventricular ejection fraction (R = –0.378; P = .036), Neuropathy Impairment Score of the Lower Limb (RS = 0.604; P = .001), Norfolk Quality of Life questionnaire (RS = 0.529; P = .003) and Karnofsky index (RS= –0.517; P = .004). A cutoff value of extracellular volume of 0.357 was diagnostic of cardiac amyloidosis with 100% sensitivity and specificity (P < .001). Extracellular volume and N-terminal pro-B-type natriuretic peptide were the only cardiac parameters that significantly correlated with neurologic scores. ConclusionsExtracellular volume quantification allows identification of cardiac amyloidosis and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. This noninvasive technique could be a useful tool for early diagnosis of cardiac amyloidosis and to track cardiac and extracardiac amyloid disease.Full English text available from: www.revespcardiol.org/en

Extracellular Volume Detects Amyloidotic Cardiomyopathy and Correlates With Neurological Impairment in Transthyretin-familial Amyloidosis

Introduction and objectivesCardiac involvement determines prognosis and treatment options in transthyretin-familial amyloidosis. Cardiac magnetic resonance T1 mapping techniques are useful to assess myocardial extracellular volume. This study hypothesized that myocardial extracellular volume allows identification of amyloidotic cardiomyopathy and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. MethodsA total of 31 transthyretin-familial amyloidosis patients (19 mean age, 49 ± 12 years; 26 with the Val30Met mutation) underwent a T1 mapping cardiac magnetic resonance study and a neurological evaluation with Neuropathy Impairment Score of the Lower Limb score, Norfolk Quality of Life questionnaire, and Karnofsky index. ResultsFive patients had cardiac amyloidosis (all confirmed by 99mTc-DPD scintigraphy). Mean extracellular volume was increased in patients with cardiac amyloidosis (0.490 ± 0.131 vs 0.289 ± 0.035; P = .026). Extracellular volume correlated with age (R = 0.467; P = .008), N-terminal pro-B-type natriuretic peptide (RS = 0.846; P < .001), maximum wall thickness (R = 0.621; P < .001), left ventricular mass index (R = 0.685; P < .001), left ventricular ejection fraction (R = –0.378; P = .036), Neuropathy Impairment Score of the Lower Limb (RS = 0.604; P = .001), Norfolk Quality of Life questionnaire (RS = 0.529; P = .003) and Karnofsky index (RS= –0.517; P = .004). A cutoff value of extracellular volume of 0.357 was diagnostic of cardiac amyloidosis with 100% sensitivity and specificity (P < .001). Extracellular volume and N-terminal pro-B-type natriuretic peptide were the only cardiac parameters that significantly correlated with neurologic scores. ConclusionsExtracellular volume quantification allows identification of cardiac amyloidosis and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. This noninvasive technique could be a useful tool for early diagnosis of cardiac amyloidosis and to track cardiac and extracardiac amyloid disease.

A Comparison of Electrocardiographic Findings among the Three Main Types of Cardiac Amyloid

Early diagnosis of Cardiac Amyloidosis is critical since treatment is primarily designed to prevent further deposition of amyloid fibrils. Electrocardiographic (EKG) findings in primary (AL) amyloid are well described but less is known about EKG findings in transthyretin-related (ATTR) amyloidosis. We sought to compare EKGs among the three main types of amyloid.

Cardiac Amyloidosis Determines the Prognosis of Systemic Amyloidosis; Roles and Responsibilities of Cardiologist

Refer to the page 752-760 Cardiac amyloidosis is a prognostically critical condition, since it is a frequent cause of death in patients with systemic amyloidosis.1),2) Lee et al.3) reported, for the first time, describing systemic amyloidosis in Korea from the perspective of cardiologists. In this paper, the authors enrolled 129 systemic amyloidosis patients retrospectively from 1999 to 2011. They showed that cardiac involve was the major prognostic factor, and old age, elevation of cardiac troponin I (cTNI), left ventricular (LV) systolic dysfunction and diastolic dysfunction were independent prognostic factors in survival. All cardiac amyloidosis were confirmed to have cardiac involvement by well-established and uncontroversial criteria including mean left ventricular thickness over 12 mm and low voltage in electrocardiogram or pathologically-confirmed amyloid deposit in endomyocardial biopsy. These diagnostic criteria were closely related to poor outcome in systemic amyloidosis.3) The diagnosis and prognosis of cardiac amyloidosis still remains to be clarified, despite the development of more sensitive tools, such as delayed gadolinium enhancement (DGE) in cardiac magnetic resonance imaging (MRI) and cardiac biomarkers. In previous studies, when cardiac MRI was performed in all AL amyloidosis patients, DGE was found in 47% of the patients with normal LV wall thickness in echocardiography.4) Moreover, the level of NT-proBNP proved to be a better discriminating factor than the LV thickness (>12 mm) in echocardiography.5-8) But, it is still not clear whether we should suspect cardiac amyloidosis in patients with normal LV thickness in echocardiography or whether early diagnosis of cardiac amyloidosis improves the prognosis of the patients. Since AL type is the most common type of systemic amyloidosis, chemotherapy and autologous stem cell transplantation are the therapies of choice. As shown,3) the hematologic response in AL amyloidosis is important in improving survival.9) Without hematologic response, it is difficult to obtain the responses in other organs. Likewise, in this paper, cardiac amyloidosis patients with better response to chemotherapy showed better survival compared to the patients with a lesser response.3) Many AL amyloidosis patients achieve hematologic response with high dose of melphalan and dexamethasone therapy or autologous hematologic stem cell transplantation.10) Additionally, bortezomib-based chemotherapy can be applied to achieve hematologic response in patients without hematologic response through melphan-based chemotherapy or autologous stem cell transplantation. Therefore, there is a significant limitation in this retrospective study. The authors did not show data regarding the benefit of additional chemotherapy in patients who had no hematologic response. In the meantime, active assessment of chemotherapy response and effort to achieve hematologic response cannot be overemphasized in the treatment of AL cardiac amyloidosis. To accurately assess multi-organ involvement and treat systemic amyloidosis, an interdisciplinary approach of cardiology, hematooncology, nephrology, pathology, and laboratory medicine and more is needed. Considering that cardiac involvement is a major prognostic factor in systemic amyloidosis, cardiologists have a great responsibility and may play a pivotal role.

Comparison of right ventricular longitudinal strain imaging, tricuspid annular plane systolic excursion, and cardiac biomarkers for early diagnosis of cardiac involvement and risk stratification in primary systematic (AL) amyloidosis: a 5-year cohort study

To determine the role of assessing right ventricular (RV) function, using standard echocardiography and Doppler myocardial imaging (DMI), in the early diagnosis of cardiac amyloidosis and in the prediction of mortality. Patients with primary systemic (AL) amyloidosis seen at our institution from 1 February 2004 through 31 October 2005 (N=249) were categorized by left ventricular thickness and E' velocity and compared with 38 age- and sex-matched controls. Standard echocardiographic and DMI examination were used to measure echocardiographic parameters of RV function: systolic tissue velocity, strain rate, and strain were determined for basal and middle RV free wall segments. Patients were followed up for the endpoint of mortality. RV tricuspid annular plane systolic excursion (TAPSE) and all DMI measurements were lower in patients with AL amyloidosis and normal echocardiography results (AL-normal-echo group) than controls. A bivariate model including strain of the basal segment of the RV free wall and TAPSE was the best for distinguishing AL-normal-echo patients from controls. Male sex [hazard ratio (HR), 2.2; P=0.005], brain natriuretic peptide levels (HR 1.4; P=0.003), troponin T levels (HR 1.6; P=0.01), pleural effusion (HR 3.6; P<0.001), E/A ratio (HR 1.3; P=0.006), RV systolic pressure (HR 1.02; P=0.01), and RV strain rate of the middle segment (HR 1.3; P=0.02) were independent predictors of death. DMI measures of the RV can identify early impairment of cardiac function or stratify risk of death in patients with AL amyloidosis. Further studies with longer follow-up are warranted to confirm these results.