scholarly journals P825 Multi-modality imaging for noninvasive diagnosis of transthyretin amyloid cardiomyopathy-single centre experience

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Gawor ◽  
J Wnuk ◽  
P Michalek ◽  
M Marczak ◽  
A Teresinska ◽  
...  
Keyword(s):  
Heart Failure ◽  
Wall Thickness ◽  
Age Of Onset ◽  
Troponin T ◽  
Severe Aortic Stenosis ◽  
Wild Type ◽  
Maximal Wall Thickness ◽  
Amyloid Deposits ◽  
Right Ventricular Wall ◽  
Amyloid Cardiomyopathy

Abstract Background Thransthyretin amyloidosis (ATTR) is a rare progressive disease that may present as heart failure with preserved ejection fraction, severe aortic stenosis, hypertrophic cardiomyopathy (HCM) or resctrictive cardiomyopathy. There are two types of ATTR: hereditary ATTR (hATTR) caused by mutations in the TTR gene and wild-type ATTR (wtATTR) resulting from deposition of wild-type TTR protein. Purpose We describe the clinical heterogeneity of ATTR patients from our centre diagnosed noninvasively in 2018-2019. Methods All patients presented intensive cardiac uptake at 99mTc-DPD scintigraphy. Light chain amyloidosis was excluded. Results 8 patients were diagnosed with ATTR (Table 1). Three unrelated male patients were diagnosed with hATTR due to rare mutations: 2 of them had Phe33Leu, 1 patient had Glu89Lys mutation. Five patients (males) were diagnosed with wtATTR. Age of onset differed among the patients. Characteristic clinical features included cardiomyopathy with increased left and right ventricular wall thickness. Only 2 patients had restrictive filling pattern, 3 patients had atrial fibrillation. Laboratory examination showed increased level of troponin T and NT-proBNP. Three patients had bilateral carpal tunnel syndrome. Thanks to DPD-scintygraphy we excluded ATTR in two patients with false-positive results of histological exam for TTR-related amyloid deposits. Conclusions Although ATTR is known for its broad clinical spectrum, patients from our center presented mostly as HCM phenocopies but in different stages of heart failure. Appropriate diagnosis of ATTR is crucial and have direct therapeutic impact. Echocardiography raise the suspicion of amyloid cardiomyopathy, while other imaging technique (DPD-scintigraphy) confirm it or exclude it in noninvasive way. Patient 1 2 3 4 5 6 7 8 Mutation Glu89Lys Phe33Leu Phe33Leu wild type wild type wild type wild type wild type Sex male male male male male male male male Age of onset 57 56 55 77 78 80 77 76 Electrocardiogram AF low QRS voltage low QRS voltage AF, RBBB LVH LVH pseudoinfarct pattern, low QRS voltage AF, LVH Maximal wall thickness [mm] 23 20 18 28 22 23 18 20 LVEF% 45 40 40 60 65 60 45 55 Asymmetric hypertrophy pattern + - - - + + - + NYHA III II II II III II II II NT-proBNP pg/ml 2122 1200 1500 2755 222 2630 2426 hs-Troponin T ng/l 50 98 42 65 35 63 64 Abstract P825 Figure 1

Cardiac amyloidosis

ESC CardioMed ◽  
2018 ◽  
pp. 1545-1549
Author(s):  
Martha Grogan
Keyword(s):  
Heart Failure ◽  
Median Survival ◽  
Cardiac Amyloidosis ◽  
Beta Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Converting Enzyme Inhibitors ◽  
Right Ventricular Wall ◽  
Immunoglobulin Light Chain Amyloidosis

Cardiac amyloidosis is an important cause of heart failure and cardiac arrhythmias, yet cardiologists often miss the diagnosis. Immunoglobulin light-chain amyloidosis (AL) is relatively rare, but likely underdiagnosed. The median survival of untreated patients with cardiac AL is 6 months after the onset of heart failure, highlighting the importance of early diagnosis. Wild-type transthyretin amyloidosis (ATTR) is increasingly recognized, especially in males over the age of 60 years. Although the clinical course of wild-type ATTR is more indolent, the median survival is approximately 3.5 years from diagnosis. Typical echocardiographic findings of increased left and right ventricular wall thickness, diastolic dysfunction, and pericardial effusion may suggest cardiac amyloidosis, along with abnormal delayed gadolinium enhancement and difficulty nulling the myocardium on cardiac magnetic resonance imaging. For AL, a tissue diagnosis is required. In contrast, ATTR may be diagnosed non-invasively with grade 2/3 uptake by nuclear scintigraphy in the absence of a monoclonal protein. Treatment of cardiac amyloidosis is entirely dependent on the type of amyloid and is directed at the underlying precursor protein or disrupting existing deposits. Cardiac care is supportive and challenging. Standard heart failure medications such as beta blockers and angiotensin-converting enzyme inhibitors are not routinely indicated and often cause haemodynamic deterioration. Outcomes of source-directed therapy for AL are improving and several clinical trials of treatment for ATTR are ongoing.

scholarly journals Transthyretin amyloid cardiomyopathy in women: frequency, characteristics, and diagnostic challenges

2020 ◽  
Vol 26 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Marianna Bruno ◽  
Adam Castaño ◽  
Arianna Burton ◽  
Justin L. Grodin
Keyword(s):  
Wall Thickness ◽  
Amyloid Fibrils ◽  
Posterior Wall ◽  
Pooled Analysis ◽  
Left Ventricular ◽  
Wild Type ◽  
Eligibility Criteria ◽  
Posterior Wall Thickness ◽  
Life Threatening ◽  
Amyloid Cardiomyopathy

AbstractTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium, resulting in cardiac structural and functional abnormalities and ultimately heart failure. Disease frequency is reportedly lower in women than men, but sex-related differences have not been well established. We conducted a systematic literature review (SLR), based on PRISMA-P guidelines and registered with PROSPERO, to assess whether the epidemiology and clinical presentation of ATTR-CM differ between women and men. MEDLINE, Embase, and Cochrane databases and selected conference proceedings were searched (August 16, 2019) to identify observational and clinical studies reporting sex-specific data for patients with wild-type or hereditary ATTR-CM. Of 193 publications satisfying final eligibility criteria, 69 studies were included in our pooled analysis. Among the 4669 patients with ATTR-CM analyzed, 791 (17%) were women, including 174 (9%), 366 (29%), and 251 (18%) in studies of wild-type, hereditary, and undefined ATTR-CM, respectively. Data available on disease characteristics were limited and very heterogeneous, but trends suggested some cardiac structural/functional differences, i.e., lower interventricular septal and posterior wall thickness and left ventricular (LV) end diastolic diameter, and higher LV ejection fractions, in women versus men across ATTR-CM subtypes. Because LV wall thickness > 12 mm is generally the suggested threshold for ATTR-CM diagnosis in both sexes, smaller cardiac anatomy in women with the disease may lead to underdiagnosis. Additional research and studies are needed to elucidate potential disparities between sexes in ATTR-CM frequency, clinical characteristics, and underlying biological mechanisms. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) database of the University of York (CRD42019146995).

scholarly journals A machine learning model for identifying patients at risk for wild-type transthyretin amyloid cardiomyopathy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ahsan Huda ◽  
Adam Castaño ◽  
Anindita Niyogi ◽  
Jennifer Schumacher ◽  
Michelle Stewart ◽  
...  
Keyword(s):  
Machine Learning ◽  
Heart Failure ◽  
At Risk ◽  
Cardiac Amyloidosis ◽  
Learning Model ◽  
Wild Type ◽  
Derivation Cohort ◽  
Machine Learning Model ◽  
Patients At Risk ◽  
Amyloid Cardiomyopathy

AbstractTransthyretin amyloid cardiomyopathy, an often unrecognized cause of heart failure, is now treatable with a transthyretin stabilizer. It is therefore important to identify at-risk patients who can undergo targeted testing for earlier diagnosis and treatment, prior to the development of irreversible heart failure. Here we show that a random forest machine learning model can identify potential wild-type transthyretin amyloid cardiomyopathy using medical claims data. We derive a machine learning model in 1071 cases and 1071 non-amyloid heart failure controls and validate the model in three nationally representative cohorts (9412 cases, 9412 matched controls), and a large, single-center electronic health record-based cohort (261 cases, 39393 controls). We show that the machine learning model performs well in identifying patients with cardiac amyloidosis in the derivation cohort and all four validation cohorts, thereby providing a systematic framework to increase the suspicion of transthyretin cardiac amyloidosis in patients with heart failure.

scholarly journals Súlyos szívelégtelenség hátterében álló transthyretin-amyloidosis elkésett diagnózisa

2021 ◽  
Vol 51 (2) ◽  
pp. 131-139
Author(s):  
Viktória Nagy ◽  
Gergely Rácz ◽  
Bence Radics ◽  
Lidia Hategan ◽  
Hedvig Takács ◽  
...  
Keyword(s):  
Heart Failure ◽  
Wall Thickness ◽  
Heart Muscle ◽  
Low Voltage ◽  
Troponin T ◽  
Diagnostic Delay ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Transthyretin Amyloidosis ◽  
Familial Form

Several heart muscle diseases can cause heart failure, the etiological diagnosis of which may serve the basis of targeted, tailored, effective personalized therapy. Such a heart muscle disease is transthyretin amyloidosis (ATTR) which is an infiltrative disorder affecting most frequently the heart and peripheral nerves, due to the accumulation of transthyretin protein. Deposition of mutant transthyretin, due to mutations in the TTR gene encoding for transthyretin, occurs in the familial form of the disease (hATTR), while in senile amyloidosis, wild-type transthyretin accumulates (wtATTR). We report on a 79-years-old male patient who presented 9 years before because of novel onset atrial fibrillation. Echocardiography at that time showed severe concentric left ventricular hypertrophy which progressed through the years. Laboratory values displayed increased liver enzymes and troponin T levels. He was hospitalized several times because of left- and later right-sided heart failure, with increasing tendency towards hypotension. At last admission he was admitted to us after suffering syncope at home necessitating cardiopulmonary resuscitation. Transthoracic echocardiography showed severe, concentric biventricular hypertrophy (LV wall thickness 22 mm, RV wall thickness 12 mm), with depressed LV and RV function, apical sparing, and low cardiac output. Taking low voltage, seen on ECG, and other anamnestic data into consideration, the suspicion of ATTR amyloidosis was raised. The patient died after a short observational period due to intractable heart failure. Autopsy and histology revealed systemic amyloidosis, affecting predominantly the heart which was interpreted as wtATTR according to immunohistochemistry, negative TTR gene sequencing and the lack of monoclonal gammopathy. Our case illustrates the importance of the diagnostic delay which is very frequently encountered in TTR amyloidosis. Features of ATTR which includes the multidisciplinary nature of assessment, specialized diagnostic modalities and unique therapy call for the need of specialized diagnostic centers.

scholarly journals The predicting system of prognosis for transthyretin amyloid cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
N.N Nakashima ◽  
S.T Takashio ◽  
M.M Morioka ◽  
M.N Nishi ◽  
K.H Hirakawa ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Troponin T ◽  
Univariate Analysis ◽  
High Sensitivity ◽  
Japanese Patients ◽  
Wild Type ◽  
Roc Curve Analysis ◽  
Staging Systems ◽  
Amyloid Cardiomyopathy ◽  
Group 2

Abstract Background The staging systems for transthyretin amyloid cardiomyopathy (ATTR-CM) by high sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) are established. However, this system is not validated in Japan. Purpose The aim of study was to validate and modify the predicting system by BNP, hs-cTnT and eGFR of prognosis for Japanese patients with ATTRwt-CM. Method We evaluated in 158 consecutive patients with wild-type ATTR-CM. Univariate analysis revealed that increased hs-cTnT and B-type natriuretic peptide (BNP) levels and impaired renal function at diagnosis were associated with poor prognosis. We defined best cutoff value as follows by ROC curve analysis; hs-cTnT >0.0565 ng/mL, BNP >285 pg/mL and eGFR <45 mL/min. We scored the index by adding 1 point for each factor and divide into low score group (0–1 point) and high score group (2–3 points). Result As shown figure, high score was associated with increased all-cause mortality and heart failure rehospitalization (log rank; P<0.001, respectively). Conclusion This simple scoring system by hs-cTnT, BNP and eGFR, was useful for predicting prognosis in patients with wild-type ATTR-CM. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals P677 When to look for wtTTR amyloidosis in heart failure: increasing chances of positive gammagraphic study

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
J Ibero ◽  
A Riesgo ◽  
M Rodriguez ◽  
M Morales ◽  
J Muniz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Wall Thickness ◽  
Troponin T ◽  
Interventricular Septum ◽  
Mean Value ◽  
Left Ventricular ◽  
P Value ◽  
Negative Results ◽  
Nyha Classification ◽  
Grade 3

Abstract Introduction Wild type transtirretin (wtATTR) amyloidosis has become increasingly recognized as a major cause for heart failure (HF). Diagnosis requires complex work up such as DPD scintigraphy (DPDs). Availability of DPDs is limited urging to identify factors to increase its diagnostic rentability. Methods Retrospective study of HF patients between 2013 and 2019 with suspected wtATTR and DPDs was performed. Baseline characteristics, biomarkers, EKG findings, TTE parameters (LVEF, LV diastolic function, TAPSE, interventricular septum (IVS), LV mass (LVM), relative LV wall thickness (RWT), indexed LVTD volume and diameter, indexed LA diameter (iAPLAD)) and DPDs results were studied. Two groups were created according to DPDs (SP those with positive results for amyloidosis and SN those with negative results). For statistical SPSS v.21 was used. Results 37 patients were studied. In our population 54% had positive DPDs for amyloidosis. Among SP patients 50% were classified as grade 2 of Perugini classification meanwhile 50% were grade 3; mean value of heart to contralateral ratio was 2,73 ± 0,8. There were no differences in NYHA classification. Differences among SP and SN patients are reflected in Table 1. Conclusions In our population SP was found to have higher biomarkers values and higher IVS, LVM, RWT and iAPLAD with poorer RV function. Further investigation is needed in order to confirm our result and identify prognostic factors. Table 1: Results Total (37) PS (20) PN (17) p value Age (Y) 78 ± 7,9 80 ± 6,5 75,29 ± 8,7 0,05 Gender (male) (%) 30 (8) 19 (95) 11(64) 0,11 Carpal tunnel sdr (%) 3(8) 3 (15) 0 (0) 0,09 Systolic blood pressure (x ± sd) 127 ± 21 118 ± 18 138,5 ± 19 <0,01 ProBNP (x ± sd) 3596 ± 4002 4615 ± 4538 1761 ± 1927 <0,05 Troponin T (x ± sd) 132 ± 360 66,4 ± 35 43 ± 39 0,09 Pseudoinfarction pattern (%) 26 (70) 17 (85) 9 (52) <0,05 IVS (mm) (x ± sd) 14,6 ± 4,5 16,6 ± 5,3 13 ± 3 <0,01 LVM (g/m2) (x ± sd) 142,5 ± 68 180 ± 80 111 ± 32 <0,01 RWT (x ± sd) 0,68 ± 0,42 0,8 ± 0,24 0,56 ± 0,5 <0,01 LVEF (%) (x ± sd) 57,4 ± 11 54 ± 12 60 ± 10 0,12 iAPLAD (mm/m2) (x ± sd) 25,4 ± 6 28,7 ± 6 22,7 ± 4,3 <0,01 TAPSE (mm) (x ± sd) 18,6 ± 5 16,1 ± 4 20,6 ± 5 <0,05 IVS = interventricular septum; LVM = left ventricular mass; RWT = relative wall thickness; iAPLAD= indexed anteroposterior left atrium diameter.

scholarly journals Bone scintigraphy in the diagnosis of transthyretin amyloidosis: a different performance in Portuguese hereditary variant?

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A F Dias De Frias ◽  
P Rodrigues ◽  
R Costa ◽  
A Campinas ◽  
A Pereira ◽  
...  
Keyword(s):  
Bone Scintigraphy ◽  
Wall Thickness ◽  
Troponin T ◽  
Statistical Significance ◽  
Renal Involvement ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Visual Score ◽  
Positive Scan ◽  
Myocardial Involvement

Abstract Introduction Bone scintigraphy using radioactive technetium-99m and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) has been increasingly used to diagnose myocardial involvement of mutated or wild-type transthyretin amyloidosis (ATTR). However, most studies that proved a high sensitivity and specificity of the technique were not in patients with the “Portuguese variant” (Val30Met) mutation in transthyretin (TTR). Other authors had already suggested that in these patients the DPD scan could be less accurate. Methods Observational study of patients referred to Cardiology clinic with suspicion of ATTR cardiomyopathy. We only included patients with data from echocardiogram and DPD scan. For statistical analyses, SPSS was used, p<0.05 for statistical significance. Logistic regressions were used to test an association between DPD result and different covariates. Results Of 273 patients referred with suspicion of cardiac ATTR, we studied 97 patients that did an echocardiogram and a DPD scan. Among the 75 cases with mutated TTR (Val30Met), median age was 36 (IQR 34) and 60% were males. 60 had increased ventricular wall thickness (IVWT) >12 mm, but only 24 had a positive DPD (defined as a visual score >2). Even though a higher wall thickness was associated with a positive DPD (p=0.004), 18 patients with a negative scan had IVWT >14 mm. The DPD results was significantly associated with prior liver transplantation (LT) – p<0.001; 95% CI (7.1; 503.6) – and age at first symptoms – p<0.001; 95% CI (1.036; 1.113); 66.7±10.5 versus 34.8±10.2 years-old for those with and without a positive scan, respectively. Interestingly, fewer patients with a positive scan had neurologic symptoms (74% versus 96%, p=0.009), ophthalmologic, urologic or renal involvement, even though creatinine clearance was on average lower (p=0.01). We did not find a significant association between DPD result and sex, conduction disorders, NT-proBNP, troponin T or treatment with tafamidis. Patients on tafamidis had on average lower IVWT, independent of age (median of 13 versus 14 mm; p=0.020). 4 patients with negative DPD did an endomyocardial biopsy, that was positive for amyloid in 3 cases. In comparison, in the 22 cases with wild-type TTR, there were significantly more males (86%) and patients were older (median age was 81 (IQR 9)). All patients had IVWT (that was significantly higher than in mutated ATTR) and DPD scan was negative in only 2 patients (that had a visual score of 1). Systolic dysfunction was significantly more frequent (59% versus 8%). The occurrence of death or hospitalization for heart failure was significantly higher. Conclusions DPD-scintigraphy seems more sensitive in patients with late onset mutated ATTR or with wild-type ATTR. It is less accurate in early onset patients with Val30Met mutation and particularly if they underwent LT. In those patients, further investigation is needed before excluding myocardial involvement. FUNDunding Acknowledgement Type of funding sources: None.

Heart Failure Complicated by Alveolar Hemorrhage due to Vascular Collapse and Amyloid Deposits in Wild-Type Transthyretin Amyloidosis

Cardiology ◽  
2016 ◽  
Vol 135 (4) ◽  
pp. 216-220 ◽  
Author(s):  
Yasutoshi Kido ◽  
Masao Takahashi ◽  
Nobuaki Fukuma ◽  
Takayuki Kawata ◽  
Atsushi Tanaka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Bronchial Artery ◽  
Clinical Manifestations ◽  
Alveolar Hemorrhage ◽  
Vascular Involvement ◽  
Amyloid Angiopathy ◽  
Sequencing Analysis ◽  
Wild Type ◽  
Oxygen Saturation Level ◽  
Amyloid Deposits

The main clinical manifestations of wild-type transthyretin (TTR)-related amyloidosis are progressive heart failure and neuropathy. There have been some reports on cerebral hemorrhage due to cerebral amyloid angiopathy in patients with TTR-related amyloidosis, but little is known about the vascular involvement in other organs. A 77-year-old woman experienced heart failure and was admitted for deteriorating heart failure status. Echocardiography showed diffuse hypokinesis of the left ventricle with biventricular wall thickness. On the 12th hospital day, the blood oxygen saturation level suddenly dropped and, despite oxygen supplementation and intensive care, the patient died. An autopsy revealed systemic deposition of amyloids which were immunolabeled by an anti-TTR antibody. Furthermore, gene-sequencing analysis showed no evidence of TTR gene mutations. The patient was diagnosed postmortem with wild-type TTR-related amyloidosis. Pathological findings revealed alveolar hemorrhage of the lung. Massive amyloid deposits were present in the vessels, and collapsed internal elastic laminae with lymphocyte infiltration were observed at the site of amyloid deposits in the bronchial artery, suggesting that deposits with inflammation might cause the collapse of the bronchial artery and lead to hemorrhage. In amyloidosis patients who suffer heart failure, there is the potential for vascular collapse caused by the accumulation of amyloid deposits with inflammation.

Combination of Huangqi Granule and Rosuvastatin Improves the Cardiac Function in Heart Failure

2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Posterior Wall Thickness

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.

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