scholarly journals Genome silencer therapy leading to “regression” of cardiac amyloid load on cardiovascular magnetic resonance—a case report

2021 ◽  
Author(s):  
Anca Florian ◽  
Michael Bietenbeck ◽  
Anna Hüsing-Kabar ◽  
Matthias Schilling ◽  
Hartmut H Schmidt ◽  
...  
Keyword(s):  
Case Report ◽  
Early Death ◽  
Pathological Process ◽  
Left Ventricular ◽  
Disease Manifestation ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Amyloid Deposits ◽  
Short Period ◽  
Amyloid Load

Abstract Background Hereditary or variant transthyretin amyloidosis (ATTRv) is a progressive disease manifesting with neuropathy and/or cardiomyopathy. An early and accurate diagnosis of cardiac amyloidosis is a prerequisite for timely and appropriate patient management, including anti-amyloid therapies, as it is associated with heart failure, conduction disease and arrhythmias, leading to reduced quality of life and early death. Case Summary We present the case of an ATTRv male patient presenting with a mixed amyloidosis phenotype (neuropathy and cardiomyopathy). Cardiac disease manifestation comprised tachyarrhythmias (atrial fibrillation) and conduction abnormalities (AV-block) in addition to segmental left ventricular (LV) hypertrophy (septal wall) due to regionally pronounced amyloid deposits in the basal LV myocardium. Interestingly, by means of serial CMR studies, we were able to demonstrate an impressive and unexpected improvement of cardiomyopathy findings within a relatively short period-of-time after implementation of genome-silencer therapies. Discussion This is our second case report that showed ATTRv cardiomyopathy reversal under anti-amyloid therapy—documented by multiparametric CMR. Our findings support the hypothesis that amyloid infiltration leading to cardiomyopathy is not an irreversible pathological process—but rather a dynamic one, that cannot only be stopped but even reversed (to a certain degree) by currently emerging anti-amyloid therapies. Moreover, the role of serial multi-parametric CMR imaging for surveillance of cardiomyopathy dynamics under these therapies is nicely illustrated.

scholarly journals Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3854-3858 ◽  
Author(s):  
Giovanni Palladini ◽  
Francesca Lavatelli ◽  
Paola Russo ◽  
Stefano Perlini ◽  
Vittorio Perfetti ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Early Death ◽  
Left Ventricular ◽  
Light Chains ◽  
Type B ◽  
Free Light Chains ◽  
Cardiac Amyloid ◽  
Amyloid Deposits ◽  
Ventricular Wall Thickness ◽  
Simultaneous Decrease

N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant. Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL. In patients (n = 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P = .01). The reduction of NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P = .04). Left ventricular wall thickness decreased by at least 2 mm in 3 of 20 patients in whom NT-proBNP improved. Fifteen patients died. Thirteen of them, in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months. The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and improved survival. Patients in whom chemotherapy fails to induce such a decrease are at risk of early death. Cardiac function in AL can rapidly improve due to a reduction of the circulating amyloidogenic precursor, despite the amount of cardiac amyloid deposits remaining apparently unaltered, as measured by echocardiography.

Cutaneous lymphatic amyloid deposits in 'Hungarian-type' familial transthyretin amyloidosis: a case report

2002 ◽  
Vol 146 (4) ◽  
pp. 674-679 ◽  
Author(s):  
T. Harkany ◽  
F. Garzuly ◽  
G. Csanaky ◽  
P.G.M. Luiten ◽  
C. Nyakas ◽  
...  
Keyword(s):  
Case Report ◽  
Transthyretin Amyloidosis ◽  
Amyloid Deposits

scholarly journals Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis

2021 ◽  
Author(s):  
Angela Pucci ◽  
Alberto Aimo ◽  
Veronica Musetti ◽  
Andrea Barison ◽  
Giuseppe Vergaro ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Endomyocardial Biopsy ◽  
Cardiac Amyloidosis ◽  
Troponin T ◽  
Tissue Sample ◽  
Extracellular Volume ◽  
Left Ventricular ◽  
Transthyretin Amyloidosis ◽  
Amyloid Deposits

Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods and Results We included all patients diagnosed with amyloid light‐chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda‐positive AL was found in 14 of 19 AL cases (38%) and kappa‐positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume ( r =0.661, P =0.001). The combined amyloid and fibrosis extent correlated with high‐sensitivity troponin T ( P =0.035) and N‐terminal pro‐B‐type natriuretic peptide ( P =0.002) serum levels. Conclusions Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.

scholarly journals Cardiac transthyretin amyloidosis 99mTc-DPD SPECT correlates with strain echocardiography and biomarkers

2020 ◽  
Author(s):  
Viktor Löfbacka ◽  
Jan Axelsson ◽  
Björn Pilebro ◽  
Ole B. Suhr ◽  
Per Lindqvist ◽  
...  
Keyword(s):  
Single Photon ◽  
Troponin T ◽  
Photon Emission ◽  
Cardiac Biomarkers ◽  
Emission Computed Tomography ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Amyloid Load ◽  
Photon Emission Computed Tomography ◽  
Strain Echocardiography

Abstract Purpose Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters. Methods Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers. Results Statistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPDload had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP. Conclusions In patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

scholarly journals Сardiopylmonary transthyretin amyloidosis

2020 ◽  
Vol 9 (4) ◽  
pp. 71-76
Author(s):  
Z.V. Gioeva ◽  
◽  
A.A. Ephiev ◽  
Keyword(s):  
Case Report ◽  
Subcutaneous Fat ◽  
Clinical Manifestations ◽  
Pulmonary Involvement ◽  
Pathological Process ◽  
Specific Information ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Autopsy Diagnosis ◽  
Pulmonary Amyloidosis

Wild type transthyretin amyloidosis (ATTRwt) affects a number of target organs, most commonly the heart. Over the last years, autopsy findings revealed that the lungs are involved in the pathological process more frequently than diagnosed in premortem cases. Due to the nonspecific nature of ATTRwt clinical manifestations and the presence of multiple concomitant conditions in elderly people, the majority of patients are diagnosed at a late stage or the disease is overlooked. As a result, ATTRwt has emerged as a previously underestimated cause of morbidity and mortality in the older age group. This article presents a clinical case report describing an 88-year-old female patient with generalized transthyretin amyloidosis characterized by predominant cardiac and pulmonary involvement. The paper elucidates the difficulties associated with premortem diagnosis of this type of amyloidosis which include the absence of amyloid deposits in biopsy specimens from the rectum and subcutaneous fat. The specific information in this case report is focused on the discrepancy between clinical and autopsy diagnosis. Keywords: wild type transthyretin amyloidosis, cardiac amyloidosis, pulmonary amyloidosis, senile amy-loidosis, chronic heart failure

Atypical Takotsubo Cardiomyopathy with Hypokinetic Left Mid-ventricle and Apical Wall Sparing: A Case Report and Literature Review

2020 ◽  
Vol 16 (3) ◽  
pp. 241-246
Author(s):  
Dipesh Ludhwani ◽  
Belaal Sheikh ◽  
Vasu K Patel ◽  
Khushali Jhaveri ◽  
Mohammad Kizilbash ◽  
...  
Keyword(s):  
Case Report ◽  
Takotsubo Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Obstructive Coronary Artery Disease ◽  
Left Ventricular ◽  
Reduced Ejection Fraction ◽  
Coronary Syndrome ◽  
Normal Left Ventricular ◽  
Artery Disease

Background: Takotsubo Cardiomyopathy (TTC) is an uncommon cause of acute reversible ventricular systolic dysfunction in the absence of obstructive Coronary Artery Disease (CAD). Typically manifesting as apical wall ballooning, TTC can rarely present atypically with apical wall sparing. Case report: A 62-year-old female presented with complaints of chest pain and features mimicking acute coronary syndrome. Coronary angiogram revealed no obstructive CAD and left ventriculogram showed reduced ejection fraction, normal left ventricular apex and hypokinetic mid-ventricles consistent with atypical TTC. The patient was discharged home on heart failure medications and a follow-up transthoracic echocardiogram demonstrated improved left ventricular function with no wall motion abnormality. Conclusion: This case report provides an insight into the diagnosis and management of TTC in the absence of pathognomic features.

Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Amyloidosis ◽  
T1 Mapping ◽  
Group Versus ◽  
Control Group ◽  
Cardiac Amyloid ◽  
Attr Amyloidosis ◽  
Amyloid Load ◽  
The Impact

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p<0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p<0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None

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