Aims Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. We sought to characterize the structural and functional echocardiographic phenotype across the spectrum of wild-type (wtATTR-CM) and hereditary (hATTR-CM) transthyretin cardiomyopathy and the echocardiographic features predicting prognosis. Methods and results We studied 1240 patients with ATTR-CM who underwent prospective protocolized evaluations comprising full echocardiographic assessment and survival between 2000 and 2019, comprising 766 with wtATTR-CM and 474 with hATTR-CM, of whom 314 had the V122I variant and 127 the T60A variant. At diagnosis, patients with V122I-hATTR-CM had the most severe degree of systolic and diastolic dysfunction across all echocardiographic parameters and patients with T60AhATTR-CM the least; patients with wtATTR-CM had intermediate features. Stroke volume index, right atrial area index, longitudinal strain, and E/e’ were all independently associated with mortality (P < 0.05 for all). Severe aortic stenosis (AS) was also independently associated with prognosis, conferring a significantly shorter survival (median survival 22 vs. 53 months, P = 0.001). Conclusion The three distinct genotypes present with varying degrees of severity. Echocardiography indicates a complex pathophysiology in which both systolic and diastolic function are independently associated with mortality. The presence of severe AS was independently associated with significantly reduced patient survival.

Purpose of Review We summarize key features pertaining to the two most commonly encountered types of cardiac amyloidosis (CA), monoclonal immunoglobulin light chain (AL) and transthyretin type (ATTR), expanding upon the clinical application and utility of various imaging techniques in diagnosing CA. Recent Findings Advances in imaging have led to earlier identification, improved diagnosis of CA and higher discriminatory power to differentiate CA from other hypertrophic phenocopies. The application of cardiac magnetic resonance imaging (CMR) has led to a deeper understanding of underlying pathophysiological processes in CA, owing largely to its intrinsic tissue characterization properties. The widespread adoption of bone scintigraphy algorithms has reduced the need for cardiac biopsy and improved diagnostic confidence in ATTR CA. Summary As new treatments for CA are rapidly developing, there will be even greater reliance on imaging, as the requirement to diagnose disease earlier, monitor response and amend treatment strategies accordingly intensifies.

Objectives The aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality. Background The clinical significance of LA involvement in ATTR-CM is of great clinical interest. Methods Congo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other). Results There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation. Conclusions The phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis.

Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt.

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Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype (Original).

Background. 99mTc-HMDP scintigraphy has proved its efficacy in non-invasive diagnosis of cardiac amyloidosis (CA) and is currently interpreted according to the Perugini qualitative assessment. Several semi-quantitative indices have been proposed to overcome inherent possible limitations of visual grading. Our aim was to comparatively evaluate six different indices and their diagnostic performance. Methods. We retrospectively reviewed scintigraphy of 76 patients (53 ATTR, 12 AL, 11 LVH) who underwent diagnostic evaluation at our centre. ROC-curve analysis was performed to identify optimal cutoff and relative diagnostic accuracy of six different indices (of which one was proposed for the first time), both in identifying CA patients and in discriminating patients according to their Perugini score. Results. Heart/Whole-body ratios proved to be the most accurate (100%) in identifying CA patients. Heart/Pelvis ratio (with soft tissue background correction) offered acceptable accuracy (98%), with the largest area under the curve (AUC) (0.98) in discriminating patients with Perugini ‡ 2. Heart/Contralateral Lung ratio confirmed to be exposed to confounding background noise in case of simultaneous lung uptake. Heart/Skull ratio had the worst performance, with six false-negative patients in ATTR identification. Conclusion. Heart/Whole-body ratios may be robust and effective semi-quantitative indices for the evaluation of CA by means of scintigraphy (J Nucl Cardiol 2019