Concomitant Cardiac Amyloidosis Research Articles

Histological assessment of cardiac amyloidosis in patients undergoing transcatheter aortic valve replacement.

Studies have reported a strongly varying co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA). We sought to histologically determine the co-prevalence of AS and CA in patients undergoing transcatheter aortic valve replacement (TAVR). Consequently, we aimed to derive an algorithm to identify cases in which to suspect the co-prevalence of AS and CA. In this prospective, monocentric study, endomyocardial biopsies of 162 patients undergoing TAVR between January 2017 and March 2021 at the University Medical Centre Göttingen were analysed by one pathologist blinded to clinical data using haematoxylin-eosin staining, Elastica van Gieson staining, and Congo red staining of endomyocardial biopsies. CA was identified in only eight patients (4.9%). CA patients had significantly higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (4356.20 vs. 1938.00ng/L, P=0.034), a lower voltage-to-mass ratio (0.73 vs. 1.46×10-2mVm2/g, P=0.022), and lower transaortic gradients (Pmean 17.5 vs. 38.0mmHg, P=0.004) than AS patients. Concomitant CA was associated with a higher prevalence of post-procedural acute kidney injury (50.0% vs. 13.1%, P=0.018) and sudden cardiac death [SCD; P (log-rank test)=0.017]. Following propensity score matching, 184 proteins were analysed to identify serum biomarkers of concomitant CA. CA patients expressed lower levels of chymotrypsin (P=0.018) and carboxypeptidase 1 (P=0.027). We propose an algorithm using commonly documented parameters-stroke volume index, ejection fraction, NT-proBNP levels, posterior wall thickness, and QRS voltage-to-mass ratio-to screen for CA in AS patients, reaching a sensitivity of 66.6% with a specificity of 98.1%. The co-prevalence of AS and CA was lower than expected, at 4.9%. Despite excellent 1year mortality, AS+CA patients died significantly more often from SCD. We propose a multimodal algorithm to facilitate more effective screening for CA containing parameters commonly documented during clinical routine. Proteomic biomarkers may yield additional information in the future.

A wolf in sheep's clothing-aortic stenosis and cardiac amyloidosis: "RAISE"ing awareness in clinical practice.

Aesop's fable of the wolf in sheep's clothing encourages us to look beneath the exterior appearance of a situation and evaluate the truth that lies beneath. This concept should be applied when managing older patients with severe aortic stenosis. This population of patients is increasingly being identified as having concomitant cardiac amyloidosis, which is an underrecognized cause of common cardiac conditions. The presence of cardiac amyloidosis negatively affects the outcome of patients with aortic stenosis, these patients undergo transcatheter aortic valve replacement (TAVR) with increasing frequency and have a significantly higher overall mortality rate than patients with aortic stenosis alone. Although left ventricular wall hypertrophy is expected in patients with aortic stenosis, it should not be assumed that this is caused only by aortic stenosis. A suspicion of cardiac amyloidosis should be raised in patients in whom the degree of hypertrophy is disproportionate to the degree of aortic stenosis severity. The remodeling, age, injury, systemic, and electrical (RAISE) score was developed to predict the presence of cardiac amyloidosis in patients with severe aortic stenosis. This article highlights the value of increased clinical suspicion, demonstrates the use of the multiparameter RAISE score in daily clinical practice, and illustrates the scoring system with case studies. In elderly patients being considered for TAVR, systematic testing for cardiac amyloidosis should be considered as part of the preoperative workup.

Prevalence of amyloid deposition and cardiac amyloidosis in shoulder disease compared to carpal tunnel syndrome

BackgroundCardiac amyloidosis is a fatal disease of severe heart failure caused by the accumulation of amyloid in the myocardium. This disease is often advanced by the time cardiac symptoms appear; therefore, early detection and treatment are critical for a good prognosis. Recently, it has been suggested that cardiac amyloidosis is implicated in several orthopedic diseases, including carpal tunnel syndrome, which is often reported to precede cardiac dysfunction. Shoulder disease has also been suggested to be associated with cardiac amyloidosis; however, there have been no reports investigating the rate of amyloid deposition in shoulder specimens and the simultaneous prevalence of cardiac amyloidosis. Herein, we investigated the prevalence of intraoperative specimen amyloid deposition and cardiac amyloidosis in shoulder disease and carpal tunnel syndrome to determine the usefulness of shoulder specimen screening as a predictor of cardiac amyloidosis development. MethodsA total of 41 patients undergoing arthroscopic shoulder surgery and 33 patients undergoing carpal tunnel syndrome surgery were enrolled in this study. The shoulder group included rotator cuff tears, contracture of the shoulder, synovitis, and calcific tendonitis. In the shoulder group, a small sample of synovium and the long head of biceps brachii tendon were harvested, while the transverse carpal ligament was harvested from the carpal tunnel syndrome group. The intraoperative specimens were pathologically examined for amyloid deposition, and patients with amyloid deposition were examined for the presence of cardiac amyloidosis by cardiac evaluation. ResultsIn the shoulder group, three cases (7.3%) of transthyretin amyloid deposition were found, all of which involved rotator cuff tears. None of these three cases with amyloid deposition were associated with cardiac amyloidosis. When examining the specimens, the amyloid deposition rate in the long head of the biceps brachii tendon was higher than that in the synovium. In the carpal tunnel syndrome group, 12 cases (36.4%) of transthyretin amyloid deposition were observed. Of these cases, seven underwent cardiac evaluation and two were identified with cardiac amyloidosis. ConclusionsWhile the prevalence of amyloid deposition and cardiac amyloidosis in the carpal tunnel syndrome group was consistent with previous reports, the shoulder group showed a lower deposition rate and no concomitant cardiac amyloidosis. Therefore, it remains debatable whether investigating amyloid deposition in samples obtained from shoulder surgery is beneficial for the early detection of cardiac amyloidosis.

Prevalence of Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release With Amyloid Deposition.

Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on 99 mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

Effect of patisiran on myocardial deformation parameters in patients with hereditary transthyretin amyloidosis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Hereditary transthyretin amyloidosis (ATTRh) is a rare autosomal dominant disease caused by transthyretin (TTR) gene mutations. It can involve several systems on the basis of ATTR gene variant, age, duration of symptoms before diagnosis. Some TTR gene variants have a predominant cardiological or neurologic or mixed phenotype, therefore patients can have only cardiac amyloidosis or only polyneuropathy or both. Recently several advances have been performed in the diagnosis and treatment of cardiac amyloidosis, especially ATTRh amyloidosis using RNA-targeting and gene editing therapies. Particularly, patisiran is a small interfering RNAs that can be used only in patients with ATTRh polyneuropathy with or without concomitant cardiac amyloidosis (stage 1 or 2). Apollo A trial sub analysis demonstrated protective effects of patisiran on the heart. Purpose To assess the effects of patisiran on cardiac function in patients with ATTRh amyloidosis treated with patisiran. Methods a prospective study was carried out enrolling 31 subjects with ATTRh (20 men, 11 women, median age 61,7 ± 10,45 years old). 7 patients (22,6%) had cardiac amyloidosis plus polyneuropathy; 13 patients (41,9%) had only polyneuropathy without cardiac involvement; 11 patients were carriers without clinical manifestations. All patients except carriers were treated with patisiran. Cardiological evaluation including electrocardiogram and echocardiogram was performed in all patients at the time of enrollment and after an average period of 20 months of patisiran therapy. Comprehensive echocardiographic evaluation included the measurement of left ventricular global longitudinal strain (GLS), relative apical sparing, apical/basal strain ratio, myocardial work index expressed as global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), left atrial reservoir strain (PALS) and atrial stiffness (LASi). Results the group of patients with only polyneuropathy remained clinically stable over time and all echocardiographic parameters didn’t change significantly. In patients with cardiac amyloidosis, we found a significant improvement in GLS (−12,39±3,31% at baseline vs − 16,32 ± 2,84%, p value 0,03) and in LASI (1,6±0,30 vs 1±0,5, p value 0,01). GWI, GWE and GCW increased during follow-up, GWW reduced but not significantly. Also a reduction in the relative apical sparing (1,08±0,36 vs 1,05±0,25, p value 0,85) and in apical/basal strain ratio (2,5±1,4 vs 2,37±1,59, p value 0,87) was observed. No other significant changes in echocardiographic parameters were found. Conclusion Patisiran seems to be effective in stabilizing cardiac disease in ATTRh, significantly improving GLS and LASI. These new echocardiographic parameters should be used to monitor response to therapy in cardiac amyloidosis. The main limitation of our study is represented by the small sample size and to confirm our results wider studies are awaited.

High Prevalence of Cardiac Amyloidosis in Clinically Significant Aortic Stenosis: A Meta-Analysis.

There is growing evidence of coexistence of aortic stenosis (AS) and transthyretin cardiac amyloidosis (CA). Not screening AS patients at the time of hospital/clinic visit for CA represents a lost opportunity. We surveyed studies that reported the prevalence of CA among AS patients. Studies that compared patients with aortic stenosis with cardiac amyloidosis (AS-CA) and AS alone were further analyzed, and meta-regression was performed. We identified nine studies with 1,321 patients of AS, of which 131 patients had concomitant CA, with a prevalence of 11%. When compared to AS-alone, the patients with AS-CA were older, more likely to be males, had higher prevalence of carpal tunnel syndrome, right bundle branch block. On echocardiogram, patients with AS-CA had thicker interventricular septum, higher left ventricular mass index (LVMI), lower myocardial contraction fraction, and lower stroke volume index. Classical low-flow low-gradient (LFLG) physiology was more common among patients with AS-CA. Patients with AS-CA had higher all-cause mortality than patients with AS alone (33% vs. 22%, P = 0.02) in a follow-up period of at least 1 year. CA has a high prevalence in patients with AS and is associated with worse clinical, imaging, and biochemical parameters than patients with AS alone.

Abstract 11271: Post TAVR Outcomes Among Patient With Amyloidosis and Aortic Stenosis: A Meta Analysis

Introduction: Aortic stenosis (AS) is one of the most prevalent valvular heart diseases globally. As many as 16% of AS patients have underlying cardiac amyloidosis (CA). To date, there is a paucity of data on outcomes among AS with concomitant CA patients post-TAVR. Hypothesis: This study aimed to evaluate the clinical outcomes post TAVR among patients with CA. Methods: We performed a systematic literature search of databases for relevant articles from inception until June 01, 2022. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of &lt;0.05 was considered statistically significant. Results: 5 studies with 1,488 patients were involved in the final analysis. The mean age of patients among CA+AS and AS alone was (85 vs 80) years. The number of males affected with dual pathology was higher compared to AS alone (71% vs 59%). 29% of patients were having a right bundle branch block in the CA+AS group, while 12% were among AS alone. Mean IV Septal Thickness (1.53 vs 1.33), mean relative wall thickness (0.60 vs 0.40) and mean LA dimensions (5.19 vs 4.8) were higher among the CA+AS group compared with AS alone. At the mean follow up of 12 months the odds of in-hospital mortality (OR, 2.09(95% CI: 0.77-5.63), P = 0.15), stroke (OR, 0.46(95%CI: 0.06-3.60), P = 0.46), and vascular complication (OR, 0.19(95% CI: 0.01-3.40), P = 0.26) were comparable between both group. In contrast, the incidence of acute kidney injury (OR, 3.09(95% CI: 2.02-4.71), P&lt;0.001), and major bleeding (OR, 1.74(95% CI: 1.02-2.98), P = 0.04) were significantly higher among CA+AS group compared to AS group following TAVR. Conclusions: TAVR appeared to be a safe procedure among patients diagnosed with amyloidosis in aortic stenosis with a similar mortality rate between both groups of patients. Further studies should aim at determining the optimal valve replacement strategy in AS patients with concomitant CA.

Prevalence and Risk Factors of Cardiac Amyloidosis in Heart Failure: A Systematic Review and Meta-Analysis.

Heart failure (HF) is one of the leading causes of mortality worldwide. Heart failure is also one of the most common presentations of cardiac amyloidosis (CA). Contemporary epidemiological data of CA in HF patients is lacking. Hence, this systematic review and meta-analysis was conducted to determine the prevalence of amyloidosis in HF patients, and to clarify the risk factors of concomitant CA and HF. A systematic review and meta-analysis was performed. Studies were retrieved from Medline, EMBASE, Scopus and Cochrane library. The search was not restricted in time, type or language of publication. The prevalence of CA in HF grouped according to diagnostic techniques and risk factors of CA with HF was analysed. Eleven (11) studies were included, involving 3,303 patients. The pooled prevalence of CA in HF was 13.7%. The overall prevalence of CA in HF with preserved ejection fraction was 15.1%, and that of HF with reduced ejection fraction was 11.3%. The main factors associated with the diagnosis of CA in HF included older age, males, raised NT pro-BNP, increased interventricular septal thickness in diastole, apical sparing, and reduced left ventricular systolic function. A high index of clinical suspicion is required to identify HF patients with CA. Supportive investigations may be helpful when clinically correlated. A considerable proportion of HF patients have CA and certain risk factors may be helpful in increasing suspicion of CA in HF.

Echocardiographic phenotype and prognostic value of relative apical sparing of longitudinal strain pattern in severe aortic stenosis with and without cardiac amyloidosis. The AMYTAVI study

Abstract Introduction It is estimated that 15% of patients with AS have concomitant cardiac amyloidosis (CA). Left ventricular (LV) longitudinal strain (LS) pattern with relative apical sparing (RELAPS&amp;gt;1), shown as bright red in the apical segments on the polar map, has been strongly associated with CA. Its presence and its significance in AS is yet to be determined. Purpose To determine the prevalence of the RELAPS&amp;gt;1 pattern in patients with severe AS with and without concomitant CA, and to analyze the echocardiographic phenotype associated with this strain pattern and its prognostic value. Methods Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: relative apical LS (average apical LS/average basal+mid LS); SAB: (apical-septal/basal-septal LS); EFSR: (LVEF/GLS). After TAVI, a 99Tc-PYP scintigraphy and a proteinogram were performed to screen for CA. Results 324 patients were included. The mean age was 81 yo, 52% women. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Among those, 111 (46%) presented relative apical sparing (RELAPS&amp;gt;1). There were no differences in clinical characteristics between patients with RELAPS &amp;lt;1 and &amp;gt;1: similar age, sex, cardiovascular risk factors and funcional class, renal function or NT-proBNP. Among patients with RELAPS&amp;gt;1 there was more frecuently CA with uptake grade 2 and 3 on scintigraphy (15% vs. 4.5%, P=0.006) (Figure 1). RELAPS&amp;gt;1 group showed greater LV hypertrophic remodeling: thicker myocardial wall with smaller ventricular cavity, especially concentric hypertrophy; LVEF and GLS was similar, however, MAPSE and myocardial contraction fraction (MCF) were worse in RELAPS &amp;gt;1 group, and EFSR was significantly higher (4.2 vs 3.9, p=0.002). RELAPS &amp;gt;1 group had smaller aortic valve area (AVA: 0.6 vs 0.7 cm2, p=0.045), but similar transvalvular gradients due to lower stroke volume. It had larger atria and less left atrial (LA) fractional emptying, as well as higher prevalence of atrial fibrillation (AF: 41% vs 27%, p=0.03). Right ventricle (RV) size were similar, however, RV function was worse in RELAPS &amp;gt;1 group (TAPSE: 19 vs 21 mm, p=0.003; free Wall LS: −24 vs −27%, p=0.008). There was no difference in all-cause mortality at 1 year of follow-up between groups (6.4% vs. 6.3%, p=1). Figure 2 represents the morphological characteristics according to the LS phenotype. Conclusions In severe AS, RELAPS &amp;gt;1 is present in almost half of the patients. It is associated with worse cardiac remodeling, as well as higher prevalence of AF. However, it wasn't associated with higher mortality at 1 year. 1 in 7 patients with AS and RELAPS &amp;gt;1 have concomitant ATTR CA grade 2/3. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer

Unveiling cardiac amyloidosis, its characteristics and outcomes among patients with mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair

Abstract Background Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on co-existence and prognostic implications of MR and CA are currently lacking. Purpose We aimed to identify prevalence, clinical characteristics and outcomes of MR-CA compared to lone MR. Methods Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR were screened for concomitant CA at two Austrian centers using a multi-parametric approach including core-lab 99mTc-DPD bone scintigraphy and echocardiography, and immunoglobulin light-chain assessment. Transthyretin-CA (ATTR) was diagnosed by DPD (Perugini Grade-1: early infiltration; Grades-2/3: clinical CA) and absence of monoclonal protein, and light-chain-(AL)-CA via tissue biopsy. Mass spectroscopy was performed in case of conflicting immunohistochemical results. All-cause mortality and hospitalization for heart failure (HHF) served as composite endpoint. Results In total, 120 patients (76.9±8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in n=14 (11.7%; 12 ATTR, 1 AL, 1 combined ATTR/AL), and early amyloid infiltration in n=9 (7.5%). MR-CA had higher troponin levels, thicker left ventricular walls, and a higher prevalence of carpal tunnel syndrome and left anterior fascicular block compared to lone MR (all p&amp;lt;0.05). Independent predictors of MR-CA were increased posterior wall thickness, and presence of left anterior fascicular block on ECG. Procedural success (MR reduction ≥1 grade) and periprocedural complications of TEER were similar in MR-CA and lone MR (p for all=n.s.). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR-CA had worse outcomes compared to lone MR with regard to the composite endpoint (HR 2.2, 95% confidence interval [95% CI] 1.0–4.7, p=0.039), driven by a 2.5-fold higher risk for HHF (HR 2.5, 95% CI 1.1–5.9), but comparable mortality (HR 1.6, 95% CI 0.4–6.1; Graphical abstract). Conclusions Dual pathology of MR-CA is common in elderly MR patients undergoing TEER, and has worse post-interventional outcomes compared to lone MR. Given technical feasibility of TEER in MR-CA, valvular repair should be considered as an option to improve forward volume in a state with typically low output. Future studies should evaluate the prognostic benefits of TEER and CA-specific treatment in MR-CA. Funding Acknowledgement Type of funding sources: None.

Unveiling Cardiac Amyloidosis, its Characteristics, and Outcomes Among Patients With MR Undergoing Transcatheter Edge-to-Edge MV Repair

BackgroundMitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on coexistence and prognostic implications of MR and CA are currently lacking. ObjectivesThis study sought to identify the prevalence, clinical characteristics, and outcomes of MR CA compared with lone MR. MethodsConsecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR at 2 sites were screened for concomitant CA using a multiparametric approach including core laboratory 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy and echocardiography and immunoglobulin light chain assessment. Transthyretin CA (ATTR) was diagnosed by 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (Perugini grade 1: early infiltration; grades 2/3: clinical CA) and the absence of monoclonal protein, and light chain (AL) CA via tissue biopsy. All-cause mortality and hospitalization for heart failure (HHF) served as the endpoints. ResultsA total of 120 patients (age 76.9 ± 8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in 14 patients (11.7%; 12 ATTR, 1 AL, and 1 combined ATTR/AL) and early amyloid infiltration in 9 patients (7.5%). Independent predictors of MR CA were increased posterior wall thickness and the presence of a left anterior fascicular block on electrocardiography. Procedural success and periprocedural complications of TEER were similar in MR CA and lone MR (P for all = NS). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR CA had worse outcomes compared with lone MR (HR: 2.2; 95% CI: 1.0-4.7; P = 0.034), driven by a 2.5-fold higher risk for HHF (HR: 2.5; 95% CI: 1.1-5.9), but comparable mortality (HR: 1.6; 95% CI: 0.4-6.1). ConclusionsDual pathology of MR CA is common in elderly patients with MR undergoing TEER and has worse postinterventional outcomes compared with lone MR.

Cardiac amyloidosis: a changing epidemiology with open challenges

Cardiac amyloidosis (CA) is increasingly diagnosed due to the advancements made in diagnostics and therapeutics in the last decades, particularly in the field of transthyretin-related CA. Studies that have used bone scintigraphy for screening at-risk conditions have shown that about one out of ten patients with heart failure with preserved ejection fraction (HFpEF), aortic stenosis undergoing valve replacement, or hypertrophic cardiomyopathy (HCM) diagnosed later in life might have an underlying or concomitant CA. At the same time, the epidemiology of these conditions is also rapidly evolving. HFpEF has become the leading form of heart failure, and HFpEF patients are increasingly cared for in non-cardiology settings due to their older age and substantial burden of comorbidities. Aortic stenosis is increasingly treated percutaneously at earlier stages of the disease, determining a significant gain in survival. Hypertrophic cardiomyopathy is nowadays mostly diagnosed in middle-aged adults with near-normal life expectancy, with a greater chance of misdiagnosing CA as HCM or of an overlap between the two conditions. In all these contexts, the therapeutic and prognostic implications of diagnosing CA will have to be further investigated. Meanwhile, the diagnostic workup of patients with suspected CA should always be completed with the systematic exclusion of a plasma cell dyscrasia, the acquisition of tomographic imaging at bone scintigraphy, and the completion of genetic testing for transthyretin-related forms.

Bone marrow involvement by ATTR amyloid is common in cardiac amyloidosis patients and may signal advanced-stage disease

Abstract Introduction/Objective Amyloidosis encompasses a heterogeneous group of disorders characterized by abnormal deposition of misfolded proteins leading to progressive organ failure. Accurate amyloid typing is essential for proper patient management, as treatment regimens vary dramatically across different types. Bone marrow (BM) biopsy, in conjunction with fat pad aspiration/biopsy, is often the first step in patients with suspected amyloidosis. Although BM involvement by AL amyloid has been previously characterized, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid in BM. Methods/Case Report We retrospectively identified 1469 BM biopsies by querying our reference laboratory database of 19,298 specimens from myriad anatomic sites typed by mass spectrometry-based proteomics (LC-MS/MS). These were reviewed for frequency of amyloid types (N=1469), distribution of amyloid deposits (N=139), and clinical phenotypes (N=345), with particular emphases on cardiac involvement. Results (if a Case Study enter NA) We identified the following amyloid types: AL (N=1172; 79.8%), ATTR (transthyretin) (N=240; 16.3%), AH (immunoglobulin heavy chain) (N=38; 2.6%), AA (serum amyloid A) (N=17; 1.2%), and Aβ2M (β2-microglobulin) (N=2; 0.1%). ATTR deposits showed striking predilection for periosteal soft tissue and/or periosteal vessels, and rarely involved BM stroma and/or interstitial vessels, while AL variably involved these compartments. AA primarily involved interstitial vessels. Both AL and ATTR cases commonly had a monoclonal gammopathy (AL: 92.9%; ATTR: 62.5%) with concomitant cardiac amyloidosis (AL: 91.6%; ATTR: 100%). Compared to AL, ATTR patients had higher stage cardiac amyloidosis and lower overall survival. Conclusion ATTR is common in BM, constituting16.3% of cases in our cohort. Rarer amyloid types, such as AA, AH and AB2M can also occur in BM. ATTR was frequently identified in patients with concomitant monoclonal gammopathy, in whom AL may have been suspected. Although ATTR deposits have distinctive morphologic distribution, primarily involving periosteal soft tissue and/or periosteal vessels and rarely involving BM stroma and/or interstitial vessels, there is considerable morphologic overlap with AL. Therefore, it is imperative to type BM amyloidosis, preferably by LC-MS/MS, to ensure proper patient management. Furthermore, BM involvement by ATTR may be a marker for advanced stage of disease.

Different aortic valve calcium scores by computed tomography scan in patients with severe aortic stenosis and concomitant cardiac amyloidosis

Abstract Background The coexistence of cardiac amyloidosis (CA) and degenerative aortic stenosis (AS) is increasing but the diagnosis is challenging because these two conditions share a common echocardiographic phenotype (1). Different predictors have been proposed in the last few years, including clinical, ECG-graphic and echocardiographic features (2–3). Purpose To identify a new marker of concomitant CA in patients with severe AS analyzing computed tomography scan (CT). Methods 55 patients with severe AS and suspicion of concomitant CA were retrospectively enrolled. Patients with a bicuspid aortic valve, previous aortic valve replacement, or an incomplete diagnostic workup for CA were excluded. 33 patients underwent CT-scan and were included in the final analysis. Results None of the patients presented laboratory suspicion for AL amyloidosis; 12 patients (AS-CA) had positive 99m Tc-DPD bone scintigraphy (two with visual score 1, eight score 2 and two score 3), 21 patients (AS-alone) had negative bone scintigraphy. AS-CA patients had a median age of 85,5 years (versus 81,5) with only one female patient (versus 8 in the AS-alone group). AVA indexed were comparable between AS-CA and AS-alone groups (0,4 versus 0, 3 mm2/m2, p: 0.25). Stroke volume evaluated by pulsed Doppler, maximum and mean gradient were significatively lower in AS-CA group (respectively 30 versus 41 ml/m2, p: 0.017, 62 versus 74 mmHg, 0.038 and 33 versus 46 mmHg, p:0.022) with a higher percentage of low flow-low gradient aortic stenosis in AS-CA group (7 patients, 58% vs 3 patients in AS-alone 14%, p: 0.027), in line with the literature. ECG at first presentation in AS-CA group showed atrial fibrillation in 8 patients (67%), versus 2 patients in the AS-alone group (10%), and lower QRS voltages (peripheral QRS score 40 mV vs 51 mV, p-value:0.017; total QRS score 113 mV versus 155 mV, p-value: 0.005). The echocardiogram showed a more thickened IVS and PW in AS-CA patients (17 versus 15 mm, p: 0.05 and 15 versus 14 mm, p: 0.013), an augmented left ventricular mass (441 versus 356 g, p: 0.036) with a decreases longitudinal systolic function (septal S wave at TDI 4.4 versus 5.2 cm/s, p: 0.026, lateral S wave 4.1 versus 5.6 cm/s, p: 0.024) and a reduction in myocardial contraction fraction (12 versus 14%, p: 0.036). CT- aortic valve calcium was quantified by an experienced operator. A statistically significant difference between AS-CA and AS-alone groups was observed in calcium score (3345 versus 4785 Hounsfield units, p: 0.037) calcium volume (2411 versus 3626 mm2, p: 0.03) and calcium mass (687 versus 1147 g, p: 0.023) Conclusions This study is the first to our knowledge to use relative aortic valve calcium score evaluation from CT imaging to characterize patients with severe AS with or without concomitant CA in addition to the classical clinical, ECG graphic, echocardiographic parameters. CT-aortic valve calcium burner was significatively lower in patients with concomitant CA. Funding Acknowledgement Type of funding sources: None. CT scan and bone scintigraphy

Prognostic impact of suspected cardiac amyloidosis in aortic stenosis patients referred for transcatheter aortic valve implantation

Abstract Background The prevalence of cardiac amyloidosis (CA) and aortic stenosis (AS) both increase with age. Transcatheter aortic valve implantation (TAVI) expands the number of patients (P) eligible for treatment of AS, emphasizing the need to understand the prevalence of CA in AS and its prognostic associations. Echocardiography with speckle tracking has emerged as a useful method to enhance the clinical suspicion and to provide prognostic information. Purpose To estimate the prevalence of CA in P with severe AS referred for TAVI and to evaluate the impact of concomitant CA in prognosis. Methods 94 consecutive AS P who underwent TAVI with maximum left ventricular wall thickness (LVWT)&amp;gt;12 mm were retrospectively identified. Clinical data, pre TAVI echocardiographic parameters and follow up (FU) data regarding all-cause mortality and MACE (including all-cause mortality, admission for heart failure, pacemaker implantation and stroke) were analysed. We registered apical sparing pattern in bull's eye plots (ASPB), calculated relative apical longitudinal strain formula (RALS) [average apical LS/(average basal LS + mid-LS)] and ejection fraction/global longitudinal strain (EF/GLS) ratio. Results Mean age was 82.2±5.8 years (Y), with 43 men (45.7%). 27.7% were in NYHA functional class II, 64.9% in functional class III and 7.4% in functional class IV. Median EF was 57±15% and 26.6% presented EF&amp;lt;50%. Suspected CA evaluated by ASPB was found in 39 P (41.5%) and RALS &amp;gt;1 was identified in 22 P (23.4%). An EF/GLS ratio &amp;gt;4.1 was obtained in 53 P (56.4%). Over a median follow-up of 13.4±25.8 months, 28 deaths (29.8%) and 31 MACEs (33.0%) occurred. The presence of ASPB was associated with increased all-cause mortality (33.3% vs. 5.6%, p=0.002) and MACE (48.7% vs 22.2%, p=0.01). RALS&amp;gt;1 correlated also with all-cause mortality (31.8% vs. 12.5%, p=0.04) and with new bundle branch block and indication for pacemaker implantation (46.2% vs 37.0%, p=0.05). P with GLS&amp;gt;−14.8% and ASPB had significantly worse prognosis regarding all-cause mortality (p=0.003) and MACE (p=0.007). Kaplan–Meier survival analysis showed that survival was significantly worse for P with ASPB (log-rank 0.002). With multivariate Cox regression analysis, ASPB was independently associated with all-cause mortality (HR=4.49, p=0.039). Conclusions Suspected CA appears prevalent among patients with AS and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation. Funding Acknowledgement Type of funding source: None

Coronary revascularisation in cardiac amyloidosis

We present a case of coronary artery bypass grafting in a 78-year-old man with triple vessel disease and concomitant cardiac amyloidosis. Postoperatively, he developed a profound low cardiac output state and multiorgan failure. He died 3 weeks following surgery. Bypass surgery is rarely performed in patients with cardiac amyloidosis, and there is little in the literature regarding outcomes. The few published cases present a bleak picture, and hence percutaneous coronary intervention should always be preferred.

Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome.

AimsConcomitant cardiac amyloidosis (CA) in severe aortic stenosis (AS) is difficult to recognize, since both conditions are associated with concentric left ventricular thickening. We aimed to assess type, frequency, screening parameters, and prognostic implications of CA in AS.Methods and resultsA total of 191 consecutive AS patients (81.2 ± 7.4 years; 50.3% female) scheduled for transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Overall, 81.7% underwent complete assessment including echocardiography with strain analysis, electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), 99mTc‐DPD scintigraphy, serum and urine free light chain measurement, and myocardial biopsy in immunoglobulin light chain (AL)‐CA. Voltage/mass ratio (VMR; Sokolow–Lyon index on ECG/left ventricular mass index) and stroke volume index (SVi) were tested as screening parameters. Receiver operating characteristic curve, binary logistic regression, and Kaplan–Meier curve analyses were performed. CA was found in 8.4% of patients (n = 16); 15 had transthyretin (TTR)‐CA and one AL‐CA. While global longitudinal strain by echo did not reliably differentiate AS from CA‐AS [area under the curve (AUC) 0.643], VMR as well as SVi showed good discriminative power (AUC 0.770 and 0.773, respectively), which was comparable to extracellular volume by CMR (AUC 0.756). Also, VMR and SVi were independently associated with CA by multivariate logistic regression analysis (P = 0.016 and P = 0.027, respectively). CA did not significantly affect survival 15.3 ± 7.9 months after TAVR (P = 0.972).ConclusionBoth TTR‐ and AL‐CA can accompany severe AS. Parameters solely based on ECG and echocardiography allow for the identification of the majority of CA‐AS. In the present cohort, CA did not significantly worsen prognosis 15.3 months after TAVR.

1226 Prognostic impact of concomitant cardiac amyloidosis in aortic stenosis patients referred for transcatheter aortic valve implantation

Abstract Background The prevalence of cardiac amyloidosis (CA) and aortic stenosis (AS) both increase with age. Transcatheter aortic valve implantation (TAVI) expands the number of patients (P) eligible for treatment of AS, emphasizing the need to understand the prevalence of CA in AS and its prognostic associations. Echocardiography with speckle tracking has emerged as a useful method to enhance the clinical suspicion and to provide prognostic information. Purpose To estimate the prevalence of CA in P with severe AS referred for TAVI and to evaluate the impact of concomitant CA in prognosis. Methods 94 consecutive AS P who underwent TAVI with maximum left ventricular wall thickness (LVWT)&amp;gt;12 mm were retrospectively identified. Clinical data, pre TAVI echocardiographic parameters and follow up (FU) data regarding all-cause mortality and MACE (including all-cause mortality, admission for heart failure, pacemaker implantation and stroke) were analysed. We registered apical sparing pattern in bull’s eye plots (ASPB), calculated relative apical longitudinal strain formula (RALS) [average apical LS/(average basal LS + mid-LS)] and ejection fraction/global longitudinal strain (EF/GLS) ratio. Results Mean age was 82.2 ± 5.8 years (Y), with 43 men (45.7%). 27.7% were in NYHA functional class II, 64.9% in functional class III and 7.4% in functional class IV. Median EF was 57 ± 15% and 26.6% presented EF &amp;lt; 50%. Suspected CA evaluated by ASPB was found in 39 P (41.5%) and RALS &amp;gt; 1 was identified in 22 P (23.4%). An EF/GLS ratio &amp;gt; 4.1 was obtained in 53 P (56.4%). Over a median follow-up of 13.4 ± 25.8 months, 28 deaths (29.8%) and 31 MACEs (33.0%) occurred. The presence of ASPB was associated with increased all-cause mortality (33.3% vs. 5.6%, p = 0.002), new bundle branch block and indication for pacemaker implantation (46.2% vs 37.0%, p = 0.05) and MACE (48.7% vs 22.2%, p = 0.01). All-cause mortality was also higher in P with RALS (31.8% vs. 12.5%, p = 0.04). P with GLS&amp;gt;-14.8% and ASPB had significantly worse prognosis regarding all-cause mortality (p = 0.003) and MACE (p = 0.007). Kaplan–Meier survival analysis showed that survival was significantly worse for P with ASPB (log-rank 0.002). With multivariate Cox regression analysis, ASPB was independently associated with all-cause mortality (HR = 4.49, p = 0.039). Conclusions Suspected CA appears prevalent among patients with AS and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation. Abstract 1226 Figure. Kaplan–Meier curves and ASPB