Correlation Between Quantitative Uptake of 99mTC-DPD and Echocardiographic Parameters in Cardiac ATTR: A Novel Follow-Up Strategy

Aims: There has been a paradigm shift in diagnosis of cardiac transthyretin amyloidosis (ATTR) with non-invasive techniques including technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy. We evaluated structural and functional biventricular alterations by transthoracic echocardiography (TTE) and determined the correlation with 99mTc-DPD tracer uptake in ATTR.Materials and Methods: ATTR patients (wild-type, hereditary or asymptomatic transthyretin [TTR] variant carriers) with 99mTc-DPD and TTE were selected; 99mTc-DPD uptake was analyzed quantitatively. TTE assessment of left ventricle (LV) and right ventricle (RV) parameters was performed.Results: Forty ATTR patients (wild-type n = 17; hereditary ATTR and TTR variant carriers n = 23; median age 68.8 ± 22 years) were included. TTE parameters displaying good correlation with 99mTc-DPD tracer uptake included LV average wall thickness (r = 0.837), LV indexed mass (LVMI; r = 0.802), RV wall thickness (r = 0.610), average e' (r = −0.830), E/e' ratio (r = 0.786), LV global longitudinal strain (GLS; r = 0.714) and RV GLS (r = 0.632; p < 0.001 for all). Hereditary ATTR and TTR variant carriers without cardiac tracer uptake had normal echocardiographic parameters. Receiver operating characteristic curves demonstrated strong diagnostic accuracies for structural (LV wall thickness, LVMI and RV wall thickness; area under the curve (AUC) of 0.96 for all) and functional (LV and RV GLS; AUC of 0.86 and 0.88, respectively) parameters.Conclusion: Good correlations between TTE biventricular structural and functional parameters were demonstrated with quantitative 99mTc-DPD uptake. Echocardiography may potentially assume a significant role in longitudinal follow-up for monitoring disease progression and for evaluating treatment response.

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P.025 APOLLO, a phase 3 study of patisiran for the treatment of hereditary transthyretin amyloidosis (hATTR): 18-month safety and efficacy in subgroup with cardiac involvement

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2019.125 ◽

2019 ◽

Vol 46 (s1) ◽

pp. S20

Author(s):

J Vest ◽

S Solomon ◽

D Adams ◽

A Gonzalez-Duarte ◽

W O’Riordan ◽

...

Keyword(s):

Wall Thickness ◽

Gait Speed ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Phase 3 ◽

Transthyretin Amyloidosis ◽

End Diastolic Volume ◽

Life Threatening ◽

And Function ◽

Cardiac Manifestations

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.

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Asymptomatic systolic dysfunction on contemporary echocardiography in anthracycline-treated long-term childhood cancer survivors: a systematic review

Journal of Cancer Survivorship ◽

10.1007/s11764-021-01028-4 ◽

2021 ◽

Author(s):

Remy Merkx ◽

Jan M. Leerink ◽

Esmée C. de Baat ◽

Elizabeth A. M. Feijen ◽

Wouter E. M. Kok ◽

...

Keyword(s):

Risk Factors ◽

Cancer Survivors ◽

Childhood Cancer ◽

Systolic Dysfunction ◽

Global Longitudinal Strain ◽

Childhood Cancer Survivors ◽

Left Ventricular ◽

Heart Region ◽

Echocardiographic Parameters

Abstract Purpose Echocardiographic surveillance for asymptomatic left ventricular systolic dysfunction (ALVSD) is advised in childhood cancer survivors (CCS), because of their risk of heart failure after anthracycline treatment. ALVSD can be assessed with different echocardiographic parameters. We systematically reviewed the prevalence and risk factors of late ALVSD, as defined by contemporary and more traditional echocardiographic parameters. Methods We searched databases from 2001 to 2020 for studies on ≥ 100 asymptomatic 5-year CCS treated with anthracyclines, with or without radiotherapy involving the heart region. Outcomes of interest were prevalence of ALVSD—measured with volumetric methods (ejection fraction; LVEF), myocardial strain, or linear methods (fractional shortening; FS)—and its risk factors from multivariable analyses. Results Eleven included studies represented 3840 CCS. All studies had methodological limitations. An LVEF < 50% was observed in three studies in 1–6% of CCS, and reduced global longitudinal strain (GLS) was reported in three studies in 9–30% of CCS, both after a median follow-up of 9 to 23 years. GLS was abnormal in 20–28% of subjects with normal LVEF. Abnormal FS was reported in six studies in 0.3–30% of CCS, defined with various cut-off values (< 25 to < 30%), at a median follow-up of 10 to 18 years. Across echocardiographic parameters, reported risk factors were cumulative anthracycline dose and radiotherapy involving the heart region, with no ‘safe’ dose for ALVSD. Conclusions GLS identifies higher prevalence of ALVSD in anthracycline-treated CCS, than LVEF. Implications for Cancer Survivors The diagnostic and prognostic value of GLS should be evaluated within large cohorts. Protocol registration PROSPERO CRD42019126588

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Scintigraphic and echocardiographic evaluation of patients with cardiac transthyretin amyloidosis and first-degree relatives

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab111.056 ◽

2021 ◽

Vol 22 (Supplement_3) ◽

Author(s):

K Holcman ◽

P Rubis ◽

W Szot ◽

K Graczyk ◽

A Stepien ◽

...

Keyword(s):

Left Ventricle ◽

Diastolic Dysfunction ◽

Longitudinal Strain ◽

Single Photon ◽

Global Longitudinal Strain ◽

Photon Emission ◽

Tracer Uptake ◽

Emission Computed Tomography ◽

Transthyretin Amyloidosis ◽

First Degree Relatives

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Pfizer Research Grant (ID#57165999) Background Misfolding of transthyretin (TTR) is the source of two distinct forms of amyloidosis (ATTR): acquired or wild-type (ATTRwt) and hereditary (ATTRm), which is transmitted in an autosomal dominant inheritance with a variable penetrance. Types of transthyretin (TTR) gene mutations display genetic and ethnic variability. Purpose The aim of this prospective study was to assess the TTR gene variants, echocardiographic parameters and regional left ventricle 99mTc-DPD uptake among patients with ATTR and first-degree relatives. Methods We present data based on evaluation of first 25 patients (13 (52%) females), including 10 (40%) index patients with ATTR (age 66.4 ± 13 years) and 15 (60%) first-degree relatives who were studied between June 2020 and February 2021. Analysis included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, single-photon emission computed tomography (SPECT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy. Results Overall, 6 index patients were diagnosed with ATTRm and 4 with ATTRwt presenting mixed, cardiac or neuropathic phenotype. There were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys. Nine out of 10 index patients were diagnosed with amyloid cardiomyopathy (CA) with grade 2-3 tracer uptake in SPECT and symptomatic heart failure (NYHA 2.2 ± 1.1; NT-proBNP value 2224 ± 2799 pg/ml). In both ATTRm and ATTRwt there were patients presenting with either focal or diffuse tracer pattern evaluated by SPECT technique. In TTE there was marked left ventricle (LV) hypertrophy with maximum wall thickness of 22 ± 5 mm and LV mass value index value of 382 ± 111 g/m2. All patients with CA had abnormal global longitudinal strain (GLS, -14.5 ± 5%) and diastolic dysfunction (EA 1.56 ± 0.76, E/E’ 16 ± 11). None of relatives expressed tracer uptake in scintigraphy. Overall, 5 first-degree relatives were diagnosed with Phe53Leu variant, among them two patients presented with decreased GLS value. Conclusions Patients with ATTR presented in TTE with LV hypertrophy, decreased GLS value, diastolic dysfunction and grade 2-3 in scintigraphy with either focal or diffuse tracer uptake in SPECT technique. None of first-degree relatives expressed increased tracer uptake in scintigraphy. However, some of relatives who were diagnosed with pathogenic TTR variant presented with decreased GLS value.

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Global longitudinal strain as a marker for systolic function in patients with pheochromocytomas

Endocrine Related Cancer ◽

10.1530/erc-20-0137 ◽

2020 ◽

Vol 27 (10) ◽

pp. 561-570

Author(s):

Atanaska Elenkova ◽

Rabhat Shabani ◽

Elena Kinova ◽

Vladimir Vasilev ◽

Assen Goudev ◽

...

Keyword(s):

Cardiac Function ◽

Longitudinal Strain ◽

Systolic Function ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Strong Positive Correlation ◽

Echocardiographic Parameters ◽

Positive Correlations ◽

Fractional Shortening

Cardiomyopathy is a frequent complication of pheochromocytoma, and echocardiography is the most accessible method for its evaluation. The objective of this study was to assess the clinical significance of classical and novel echocardiographic parameters of cardiac function in 24 patients with pheochromocytomas (PPGL) compared to 24 subjects with essential hypertension (EH). Fourteen PPGL patients were reassessed after successful surgery. Left ventricular hypertrophy was four times more prevalent in patients with PPGL vs EH (75% vs 17%; P = 0.00005). Left ventricular mass index (LVMi) significantly correlated with urine metanephrine (MN) (rs = 0.452, P = 0.00127) and normetanephrine (NMN) (rs = 0.484, P = 0.00049). Ejection fraction (EF) and endocardial fractional shortening (EFS) were normal in all participants and did not correlate with urine metanephrines. Global longitudinal strain (GLS) was significantly lower in PPGL compared to EH group (−16.54 ± 1.83 vs −19.43 ± 2.19; P < 0.00001) and revealed a moderate significant positive correlations with age (rs = 0.489; P = 0.015), LVMi (rs = 0.576, P < 0.0001), MN (rs = 0.502, P = 0.00028) and NMN (rs = 0.580, P < 0.0001). Relative wall thickness (RWT) showed a strong positive correlation with urine MN (rs = 0.559, P < 0.0001) and NMN (rs = 0.689, P < 0.00001). Markedly decreased LVMi (118.2 ± 26.9 vs 102.9 ± 22.3; P = 0.007) and significant improvement in GLS (−16.64 ± 1.49 vs −19.57 ± 1.28; P < 0.001) was observed after surgery. ΔGLS depended significantly on the follow-up duration. In conclusion, classical echocardiographic parameters usually used for assessment of systolic cardiac function are not reliable tests in pheochromocytoma patients. Instead, GLS seems to be a better predictor for the severity and the reversibility of catecholamine-induced myocardial function damage in these subjects. RWT should be measured routinely as an early indicator of cardiac remodeling.

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Evaluation of left ventricular remodelling in young Afro-Caribbean athletes

Cardiovascular Ultrasound ◽

10.1186/s12947-019-0169-8 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

Giorgio Galanti ◽

Loira Toncelli ◽

Benedetta Tosi ◽

Melissa Orlandi ◽

Chiara Giannelli ◽

...

Keyword(s):

Body Size ◽

Wall Thickness ◽

Contractile Function ◽

Blood Pressure Response ◽

Global Longitudinal Strain ◽

Interventricular Septum ◽

Left Ventricular ◽

Ventricular Remodelling ◽

Left Ventricular Remodelling

Abstract Background Cardiac adaptation to intense physical training is determined by many factors including age, gender, body size, load training and ethnicity. Despite the wide availability of ECG analysis, with a higher presence of abnormalities in different races, echocardiographic studies on young Afro-Caribean (AA) and Caucasian athletes (CA) are lacking in literature. We aimed to assess the effect in the secondary LV remodelling of load training in young AA players compared to matched CA players. Method Seventy-seven AA and 53 CA matched soccer players (mean age 17.35 ± 0.50 and 18.25 ± 0.77 y) were enrolled. They were evaluated with echocardiography. A subgroup of 30 AA and 27 CA were followed up for a period of 4 years. The myocardial contractile function was evaluated by speckle-tracking echocardiographic global longitudinal strain (GLS). Results No significant differences were found in weight and height and in blood pressure response to maximal ergometer test in either group. In AA a higher level of LV remodelling, consisting in higher LV wall thickness, higher interventricular septum (IVS) and posterior wall (PW) thickness were found (IVS: 10.04 ± 0.14 and 9.35 ± 0.10 in AA and CA respectively, p < 0.001. PW: 9.70 ± 0.20 and 9.19 ± 0.10 mm in AA and CA respectively, p < 0.05). Strain data showed no significant differences between the two groups (22.35 ± 0.48 and 23.38 ± 0.69 in AA (n = 27) and CA (n = 25), respectively). At the beginning of the follow-up study AA showed a significantly higher left ventricular remodelling (IVS = 9.29 ± 0.3 and 8.53 ± 0.12 mm in AA and CA respectively, p < 0.002. PW = 9.01 ± 0.2 and 8.40 ± 0.20 in AA and CA respectively, p = 0.1). During the next four years of follow-up we observed a regular parallel increase in LV wall thickness and chamber diameters in both groups, proportionally to the increase in body size and LV mass. (IVS = 10.52 ± 0.17 and 9.03 ± 0.22 mm in AA and CA respectively, p < 0.001. PW: 10.06 ± 0.17 and 8.26 ± 0.19 mm in AA and CA respectively, p < 0.001). Conclusion The study shows that the ventricular remodelling observed in AA appears to be a specific phenotype already present in pre-adolescence. These data also suggest that genetic/ethnic factors play a central role in left ventricular remodelling during the first years of life in elite athletes.

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Subclinical Myocardial Dysfunction in Patients Recovered from COVID-19 Disease: Correlation with Exercise Capacity

Biology ◽

10.3390/biology10111201 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1201

Author(s):

Or Shimoni ◽

Roman Korenfeld ◽

Sorel Goland ◽

Valery Meledin ◽

Dan Haberman ◽

...

Keyword(s):

Exercise Capacity ◽

Stress Echocardiography ◽

Longitudinal Strain ◽

Myocardial Dysfunction ◽

Severe Disease ◽

Global Longitudinal Strain ◽

Echocardiographic Parameters ◽

History Of

Aims: Myocardial abnormalities are common during COVID-19 infection and recovery. We examined left (LV) and right (RV) ventricular longitudinal strain in patients who had recovered from COVID-19 and assessed the correlation with exercise capacity. Methods and results: One hundred and eighty-four consecutive patients with history of COVID-19 disease who had been referred to rest or stress echocardiography because of symptoms, mainly dyspnea and chest pain, were included in the study. These patients were compared to 106 patients with similar age, symptoms, and risk factor profile with no history of COVID-19 disease. Clinical and echocardiographic parameters, including strain imaging, were assessed. The patient’s age was 48 ± 12 years. Twenty-two patients had undergone severe disease. There were no differences in the LV ejection fraction and diastolic function between the groups. However, LV and RV global and free wall strain were significantly lower (in absolute numbers) in patients who had recovered form COVID-19 infection (−20.41 ± 2.32 vs −19.39 ± 3.36, p = 0.001, −23.69 ± 3.44 vs −22.09 ± 4.20, p = 0.001 and −27.24 ± 4.7 vs −25.43 ± 4.93, p = 0.021, respectively). Global Longitudinal Strain (GLS) < −20% was present in only 37% of post COVID-19 patients. Sixty-four patients performed exercise echocardiography. Patients with GLS < −20% had higher exercise capacity with higher peak metabolic equivalent and exercise time compared to patients with GLS ≥ −20% (12.6 ± 2 vs 10 ± 2.5 METss and 8:00 ± 2:08 vs 6:24 ± 2:03 min, p < 0.001 and p = 0.003, respectively). Conclusion: In patients, who had recovered from COVID-19 infection, both LV and RV strain are significantly lower compared to control patients. The exercise capacity of these patients correlates with LV strain values. Rest and stress echocardiography in patients with symptoms after COVID-19 infection may identify patients that need further follow up to avoid long term complications of the disease. These preliminary results warrant further research, to test the natural history of these findings and the need and timing of treatment.

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Prognostic value of layer-specific global longitudinal strain in patients undergoing coronary artery bypass grafting

European Heart Journal ◽

10.1093/eurheartj/ehab724.018 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

F S Davidovski ◽

M Lassen ◽

K Skaarup ◽

F J Olsen ◽

M Sengeloev ◽

...

Keyword(s):

Prognostic Value ◽

Longitudinal Strain ◽

Artery Bypass ◽

Global Longitudinal Strain ◽

All Cause Mortality ◽

Specific Strain ◽

Echocardiographic Parameters ◽

Multivariable Models ◽

Absolute Decrease

Abstract Background Recent improvements in speckle tracking echocardiography have made sectionalized quantification of layer-specific global longitudinal strain (GLS) possible. Prior studies have reported prognostic value of GLS in several cardiac diseases, however, the use of layer-specific strain has not been investigated in patients undergoing coronary artery bypass grafting (CABG). Purpose To determine the prognostic value of layer-specific GLS for predicting all-cause mortality after CABG. Methods In this retrospective cohort study, consecutive patients undergoing isolated CABG between 2006 and 2011 were included. The patients were followed through nation-wide registries for the endpoint of all-cause mortality. Multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics were used to assess the association between layer-specific GLS and all-cause mortality. Cumulative survival was stratified by clinical age and gender-dependent cut-off values for the layer-specific GLS, which was obtained from a large healthy population study. Results Of 641 patients included (mean age 67 years, 84% male), 70 (10.9%) died during follow-up (median 3.8 years [IQR: 2.7; 4.9 years]). Patients who died during follow-up were significantly older (71 years vs. 67 years, P = <0.001) and had a lower LVEF (46% vs. 51% P = <0.001). Endocardial GLS (GLSendo) (−14.2% vs. −16.3%, P<0.001), whole wall GLS (−12.1% vs. −13.9%, P<0.001), and epicardial GLS (GLSepi) (−10.6% vs. −12.2%, P<0.001) were all reduced in patients who died during follow-up, and patients with GLS below cut-off had a more than two-fold increased risk of all-cause mortality (Figure 1). The risk of dying increased linearly with decreasing absolute GLS for all layers (p<0.0002 for all layers), (Figure 2). In multivariable models, all layer-specific strain parameters remained significantly associated with all-cause mortality; GLSepi: HR=1.14 (1.05–1.23), p=0.002; GLS: HR=1.12 (1.04–1.20), p=0.002; GLSendo: HR=1.09 (1.03–1.16), p=0.003, per 1% absolute decrease. However, only GLSepi remained significantly associated with mortality when also adjusting for echocardiographic parameters (GLSepi: HR=1.12 (1.00–1.25), p=0.049, per 1% absolute decrease) and separately also after adjusting for the EuroScore II (GLSepi: HR=1.09 (1.00–1.18), p=0.043, per 1% absolute decrease). Conclusion Layer-specific GLS is an independent prognosticator of all-cause mortality after CABG. In multivariable models, GLSepi provided significant prognostic value after adjusting for echocardiographic parameters and EuroScore II. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Research grant from Herlev & Gentofte University Hospital's internal research funds. Figure 1. Kaplan-Meier survival estimates Figure 2. Incidence rate of all-cause mortality

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Use of echocardiography to stratify the risk of atrial fibrillation: comparison of left atrial and ventricular strain

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez240 ◽

2019 ◽

Cited By ~ 2

Author(s):

Hiroshi Kawakami ◽

Satish Ramkumar ◽

Faraz Pathan ◽

Leah Wright ◽

Thomas H Marwick

Keyword(s):

Atrial Fibrillation ◽

Predictive Value ◽

Left Atrial ◽

Global Longitudinal Strain ◽

Cryptogenic Stroke ◽

Predictive Values ◽

Lv Dysfunction ◽

Echocardiographic Parameters ◽

History Of

Abstract Aims Although both left atrial (LA) and ventricular (LV) dysfunction has been accepted as an important risk factor of atrial fibrillation (AF), usefulness of LA and LV strain has not been fully compared for prediction of AF. The aims of this study were to clarify the associations of both LA and LV strain with AF and to compare their predictive values in the risk stratification for AF. Methods and results We evaluated 531 consecutive patients (median age 67 years, 56% male), with no history of AF who underwent echocardiography after cryptogenic stroke. Standard echocardiographic parameters were measured, and speckle-tracking was used to measure LA (reservoir, pump, and conduit strain) and LV strain (global longitudinal strain, GLS). The baseline clinical and echocardiographic parameters of the patients who developed AF and those who did not were compared. Median 36 months of follow-up, 61 patients (11%) had newly diagnosed AF. LA pump strain and GLS were significantly and independently associated with AF and provided incremental predictive value over clinical and standard echocardiographic parameters. Areas under the receiver-operating curves for GLS (0.841) were comparable to LA pump (0.825) and reservoir (0.851) strain. However, predictive value of both strains was different between patients with and without LA enlargement at the time of transthoracic echocardiography screening. LA strain was more useful than LV strain in patients with normal LA volumes, while LV strain was more useful than LA strain in patients with abnormal LA volumes. Conclusion Both LA and LV strain are significantly and independently associated with AF and provide incremental predictive value over clinical and standard echocardiographic parameters. However, priorities of strain assessment are different depends on patients’ condition at the time of echocardiography.

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Abstract 2397: Morbidity and Mortality of Transthyretin (TTR) Amyloid Cardiomyopathy (ATTR-CM): Transthyretin Amyloidosis Cardiac Study (TRACS) a Prospective Evaluation

Circulation ◽

10.1161/circ.118.suppl_18.s_717-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Frederick L Ruberg ◽

Martha Skinner ◽

Antony Y Kim ◽

Steven Zeldenrust ◽

Daniel Judge ◽

...

Keyword(s):

Wall Thickness ◽

Troponin I ◽

Nyha Class ◽

Disease Diagnosis ◽

Full Cohort ◽

Transthyretin Amyloidosis ◽

Therapeutic Trials ◽

History Of ◽

Minute Walk

Background: ATTR-CM is believed to have a relatively indolent course, with a median survival of ~5 years from heart failure symptoms; however, no data exist as to the rate of progression after disease diagnosis. ATTR-CM is associated with genetic variants, including V122I (present in ~ 3.5% of African Americans), or wild-type TTR (senile systemic amyloidosis - SSA). While there is no effective treatment other than heart transplantation, therapies designed to slow or halt amyloid deposition are in development. The purpose of this study was to characterize the natural history of ATTR-CM to support future therapeutic trials. Methods: Patients with ATTR-CM due to V122I (n = 11) and SSA (n = 18), were enrolled 10.4 ± 11.9 months after diagnosis (range: 0 – 60 months) and assessed every 6 months for up to two years by echocardiography and cardiac magnetic resonance imaging (CMR), with functional capacity assessed by 6-minute walk, and biochemical profile including cardiac troponins and NT-pro-B-type natriuretic peptide (BNP). Baseline data from the full cohort (n = 29), and available data from those completing the 12 month assessment (n = 15) are presented for this on-going study. Results : At baseline, both groups were similar in terms of gender, duration of disease from diagnosis, NYHA, troponin/NT-BNP, and echo or CMR-measured LV wall thickness. SSA patients were older (mean age 76 vs. 71y, P = 0.03), Caucasian (100% vs 0%, P < 0.001), with a history of atrial fibrillation (83% vs. 27%, p = 0.003). During a mean follow-up of 442 days (30–768), there have been 7 deaths (4 V122I; 3 SSA) and 1 cardiac transplantation (SSA), and 10 of 29 (34.5%) were hospitalized at least once (90% for cardiac reasons). For those subjects with a 12 month assessment, LV ejection fraction declined by echo (2.8 %) and CMR (12 %), with minimal changes in wall thickness. Increases were seen in NT-Pro-BNP (87%) and troponin (I: 186%; T: 70%). Worsening of NYHA class occurred in 43% of patients; 6-minute walk distance decreased by 19.2%. Conclusions : Despite reports of a relatively indolent course of ATTR-CM, preliminary data from this ongoing study are the first to demonstrate that quantifiable noninvasive parameters worsen over a 1 year follow up period and are associated with adverse clinical outcomes.

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