Myocardial Work Does Not Have Additional Diagnostic Value in the Assessment of ATTR Cardiac Amyloidosis

Background: Reduced LV longitudinal strain (GLS) and increased relative apical sparing (RELAPS) and increased wall thickness have been proposed as features for transthyretin cardiac amyloidosis (ATTR-CA). Myocardial work (MW) has recently been shown as useful afterload independent disease marker, hence we aimed to investigate its use in differentiating ATTR-CA from heart failure with increased septal thickness but no cardiac amyloidosis (CA) (HFnCA). Methods: This study included patients with HF and increased septal thickness ≥ 14 mm. We included 59 patients with hereditary (ATTRv) and 27 wild type transthyretin amyloidosis (ATTRwt) described as ATTR-CA based on DPD scintigraphy. We also enrolled 30 non-amyloidosis heart failure patients with negative DPD scintigraphy, as a control group. Myocardial work (MW) was used to assess the index (GWI), constructive (GCW) and wasted (GWW) work. Relative wall thickness (RWT) and relative apical sparing (RELAPS) were tested as conventional measures. Results: The RWT and RELAPS were higher in ATTR-CA (p < 0.001) and predicted ATTR-CA (RWT; AUC = 0.84, p < 0.001) and RELAPS (AUC = 0.81, p < 0.001). MW; GWI (p = 0.04), GCW (p = 0.03), GWW (p = 0.001) were all lower in ATTR-CA compared with HFnCA but only GWW predicted ATTR-CA, (AUC = 0.75, p < 0.001). Binary logistic univariate regression analysis showed RWT (p = 0.003, β = 16.2) and RELAPS (p = 0.003, β = 2.3) to be associated with ATTR-CA but not MW. GWI and GCW correlated with NT-proBNP (p < 0.05) and Troponin (p < 0.01), but not RWT or RELAPS. Conclusion: Myocardial work had lower accuracy, compared to RWT or RELAPS, in identifying ATTR-CA but was better related to biomarkers. Thus, MW assessment is unlikely to have additional value in improving the diagnosis of heart failure due to ATTR-CA.

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Cardiac Amyloidosis Therapy: A Systematic Review

Cardiogenetics ◽

10.3390/cardiogenetics11010002 ◽

2021 ◽

Vol 11 (1) ◽

pp. 10-17

Author(s):

Franco Iodice ◽

Marco Di Mauro ◽

Marco Giuseppe Migliaccio ◽

Angela Iannuzzi ◽

Roberta Pacileo ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Cardiac Amyloidosis ◽

Restrictive Cardiomyopathy ◽

Novel Therapies ◽

Preserved Ejection Fraction ◽

Cardiac Damage ◽

Transthyretin Amyloidosis ◽

To Come ◽

Almost All

Heart involvement in Cardiac Amyloidosis (CA) results in a worsening of the prognosis in almost all patients with both light-chain (AL) and transthyretin amyloidosis (ATTR). The mainstream CA is a restrictive cardiomyopathy with hypertrophic phenotype at cardiac imaging that clinically leads to heart failure with preserved ejection fraction (HFpEF). An early diagnosis is essential to reduce cardiac damage and to improve the prognosis. Many therapies are available, but most of them have late benefits to cardiac function; for this reason, novel therapies are going to come soon.

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Cardiac amyloidosis

ESC CardioMed ◽

10.1093/med/9780198784906.003.0373 ◽

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.

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Cardiac Care of Patients with Cardiac Amyloidosis

Acta Haematologica ◽

10.1159/000506919 ◽

2020 ◽

Vol 143 (4) ◽

pp. 343-351

Author(s):

Osnat Itzhaki Ben Zadok ◽

Ran Kornowski

Keyword(s):

Heart Failure ◽

Cardiac Amyloidosis ◽

Management Strategies ◽

Treatment Strategies ◽

Multidisciplinary Care ◽

Cardiac Care ◽

Immunoglobulin Light Chain ◽

Transthyretin Amyloidosis ◽

Immunoglobulin Light Chain Amyloidosis ◽

Specific Management

Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different aspects of the heart and cardiovascular system. Amyloid-induced cardiomyopathy, clinically manifesting with heart failure and electrophysiological abnormalities, has distinct characteristics compared to non-amyloid cardiomyopathies. Accordingly, specific management strategies are required. This paper will review the cardiovascular manifestations of patients with cardiac amyloidosis and their suggested treatment strategies, emphasizing the importance of multidisciplinary care.

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P971 The echocardiographic phenotype in patients with cardiac amyloidosis and heart failure with preserved ejection fraction

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.603 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

M D M Perez Gil ◽

V Mora Llabata ◽

A Saad ◽

A Sorribes Alonso ◽

V Faga ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cardiac Amyloidosis ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Ventricular Ejection Fraction ◽

Apical Rotation ◽

Dynamic Torsion

Abstract BACKGROUND New echocardiographic phenotypes of heart failure (HF) are focused on myocardial systolic involvement of the left ventricle (LV), either endocardial and/or transmural. PURPOSE. To study the pattern of myocardial involvement in patients (p) with HF with preserved left ventricular ejection fraction (pLVEF) and cardiac amyloidosis (CA). METHODS. Comparative study of 16 p with CA and HF with pLVEF, considering as cut point LVEF > 50%, in NYHA class ≥ II / IV, and a control group of 16 healthy people. Longitudinal Strain (LS) and Circumferential Strain (CS) were calculated using 2D speckle-tracking echocardiography, along with Mitral Annulus Plane Systolic Excursion (MAPSE) and Base-Apex distance (B-A). Also, the following indexes were calculated: Twist (apical rotation + basal rotation, º); Classic Torsion (TorC): (twist/B-A, º/cm); Torsion Index (Tor.I): (twist/MAPSE, º/cm) and Deformation Index (Def.I): (twist/LS, º). We suggest the introduction of these dynamic torsion indexes as Tor.I and Def.I that include twist per unit of longitudinal systolic shortening of the LV instead of using TorC which is the normalisation of twist to the end-diastolic longitudinal diameter of the LV. RESULTS There were no differences of age between the groups (68.2 ± 11.5 vs 63.7 ± 2.8 years, p = 0.14). Global values of LS and CS were lower in p with CA indicating endocardial and transmural deterioration during systole, while TorC and Twist of the LV remained conserved in p with CA. However, there is an increase of dynamic torsion parameters such as Tor.I and Def.I that show an increased Twist per unit of longitudinal shortening of the LV in the CA group (Table). CONCLUSIONS In p with CA and HF with pLVEF, the impairment of LS and CS indicates endocardial and transmural systolic dysfunction. In these conditions, LVEF would be preserved at the expense of a greater dynamic torsion of the LV. Table LS (%) CS (%) Twist (º) TorC (º/cm) Tor.I (º/cm) Def.I (º/%) CA pLVEF (n = 16) -11.7 ± 4.2 17.2 ± 4.8 19.8 ± 8.3 2.5 ± 1.1 27.7 ± 13.5 -1.8 ± 0.9 Control Group (n = 15) -20.6 ± 2.5 22.7 ± 4.9 21.7 ± 6.1 2.7 ± 0.8 16.4 ± 4.7 -1.0 ± 0.3 p < 0.001 < 0.01 0.46 0.46 < 0.01 < 0.01 Dynamic Torsion Indexes and Classic Torion Parameters in pLVEF CA patients vs Control group.

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A Novel Paradigm Based on ST2 and Its Contribution towards a Multimarker Approach in the Diagnosis and Prognosis of Heart Failure: A Prospective Study during the Pandemic Storm

Life ◽

10.3390/life11101080 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1080

Author(s):

Radu-Stefan Miftode ◽

Daniela Constantinescu ◽

Corina Maria Cianga ◽

Antoniu Octavian Petris ◽

Amalia-Stefana Timpau ◽

...

Keyword(s):

Heart Failure ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

Control Group ◽

Diagnosis And Prognosis ◽

Test Kit ◽

Positive Correlations ◽

Lactate Levels ◽

A Prospective Study

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians’ interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.

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Rapid decline in ejection fraction and persistent elevation of troponin associated with cardiac amyloidosis

SAGE Open Medical Case Reports ◽

10.1177/2050313x20923259 ◽

2020 ◽

Vol 8 ◽

pp. 2050313X2092325

Author(s):

Temidayo Abe ◽

Eric Y Chang ◽

Gabrielle De Allie ◽

Taiwo Ajose ◽

Chukwuemeka Nwokike ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Amyloidosis ◽

Cardiac Biomarkers ◽

Rapid Decline ◽

Unique Case ◽

Transthyretin Amyloidosis ◽

Progressive Heart Failure ◽

The Mean ◽

Persistent Elevation

Cardiac amyloidosis is an increasingly recognized cause of heart failure. It remains underdiagnosed despite a significant morbidity and mortality rate. The mean survival in patients with cardiac amyloidosis is less than 1 year in untreated primary light-chain amyloidosis and less than 4 years in wild-type transthyretin amyloidosis. We report a unique case of a 78-year-old male with transthyretin cardiac amyloidosis, who presented with persistently elevated troponin and progressive heart failure unresponsive to conventional therapy. With this case, we would like to highlight the role of cardiac biomarkers in the early diagnosis of cardiac amyloidosis.

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Significance of Brain Natriuretic Peptide Measurement as a Diagnostic Indicator of Cardiac Function

Methods of Information in Medicine ◽

10.1055/s-0038-1634337 ◽

2000 ◽

Vol 39 (03) ◽

pp. 249-253 ◽

Cited By ~ 21

Author(s):

N. Iida ◽

T. Ishihara ◽

S. Waku

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Diagnostic Value ◽

Left Ventricular ◽

Control Group ◽

Healthy Control ◽

Group 5 ◽

Lv Diastolic Dysfunction

AbstractBrain natriuretic peptide (BNP) is increased in patients with heart failure due to myocardial infarction and cardiac hypertrophy, in proportion to the severity of left ventricular dysfunction. The aims of this study were to clarify the clinical features of BNP and to determine the diagnostic value of BNP for mass screening.The subjects were 818 office workers (565 males and 253 females; mean age 47 ± 12 years) who participated in a 1996 routine health check at Kansai University All individuals were examined for blood pressure, serological findings, ECG and plasma BNP level. Thirty-three males underwent 2-D echocardiography. Plasma BNP levels were measured using IRMA (immunoradiometric assay).The results were as follows: (1) BNP levels in females were higher than those in males for healthy subjects (N = 551), in each age group from 20 to 60 years. (2) BNP levels increased with age. (3) There were significant correlations between BNP level and systolic blood pressure and creatinine level. (4) There were significant differences in BNP level between the hypertensive groups with and without hypertensive ECG changes and the age-matched healthy control group. (5) Marked correlations were observed between BNP level and left ventricular wall thickness, fractional shortening, deceleration time and peak early filling velocity. (6) A BNP cut-off-point of 25 pg/ml was best for detecting LV diastolic dysfunction and LV hypertrophy. Measurement of BNP is useful for detecting asymptomatic heart failure in the general population, and is a clinical marker useful in preventing symptomatic heart failure.

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1038 Comparative assessment of phasic left atrial and regional left ventricular strain in patients with cardiac amyloidosis and LV hypertrophy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.630 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

A M Brand ◽

G Baldenhofer ◽

D Frumkin ◽

A Huebscher ◽

K Stangl ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Sensitivity And Specificity ◽

Wall Thickness ◽

Left Atrial ◽

Cardiac Amyloidosis ◽

Multivariate Logistic Regression Analysis ◽

Diagnostic Value ◽

Left Ventricular ◽

Volume Index ◽

Al Amyloidosis

Abstract Background Echocardiographic hallmarks of cardiac amyloidosis (CA), such as increased wall thickness of the LV and sparkling appearance of the myocardium, are limited by a reduced diagnostic accuracy. Purpose We sought to evaluate the diagnostic value of phasic left atrial strain alterations and of regional global longitudinal systolic LV strain (LVGLS) reductions in patients with CA and with other forms of LV hypertrophy. Methods Standard apical 4-chamber views were stored for offline analysis (Vivid E9, GE, Vingmed, Horton) in 54 patients who underwent endomyocardial biopsy for unclear LV hypertrophy. We then analyzed LVGLS as well as LA reservoir, conduit, and contraction strain using 2D speckle tracking echocardiography (2DSTE; EchoPAC software, GE). To assess regional LVGLS, the average of apical strain values / (average of mid + basal LV strain values) was calculated (relative apical sparing; RELAPS). Receiver operating characteristic (ROC) curve analyses and a multivariate logistic regression analysis were performed to investigate the diagnostic value of the respective LA and LV deformation analysis. Results CA was bioptically confirmed in 34 patients (13 TTR, 1 AA, 20 AL amyloidosis). In 18 patients, myocardial biopsy revealed other forms of LV hypertrophy, such as hypertensive heart disease (n = 2), hypertrophic cardiomyopathy (n = 12), and inflammatory myocardial diseases (n = 4). Mean septal wall thickness (17.7 ± 2.9 mm and 17.9 ± 4.3 mm) and left atrial volume index (43.8 ± 12.2 and 44.1 ± 17.2) were not different between groups. RELAPS was significantly higher in patients with CA (1.37 ± 0.94 vs. 0.86 ± 0.29, p<.007). Phasic atrial mechanics were significantly worse in CA (LA reservoir, conduit, and contraction strain 10.0 ± 5.2%, -6.5 ± 3.5%, and -5.0 ± 4.1%, respectively, in CA; and 22.7 ± 7.8%, -13.9 ± 5.2%, and -13.0 ± 5.5%, in LVH, respectively; p<.001). With an area under the curve (AUC) of 0.91, and a sensitivity and specificity of 91.2 and 84.2% for a cut-off value of <15.8%, LA reservoir strain showed a higher diagnostic accuracy in discriminating CA from LVH than the parameter RELPAS (AUC 0.74, sensitivity and specificity 60% and 71% for a cut-off of >1.0; p<.05). LA conduit and contraction strain performed significantly better than RELAPS as well (AUC 0.87 for conduit, and AUC 0.86 for contraction function; p<.001 each). Of all echocardiographic parameters, LA reservoir strain remained significantly associated with CA in a multivariate regression model. Conclusions LA strain during all three phases of the atrial cycle was significantly reduced in patients with CA compared to other forms of LVH, and showed a markedly higher diagnostic accuracy than regional LV strain analysis, with LA reservoir strain showing highest discriminative value. The assessment of LA strain, as part of a comprehensive echocardiographic assessment, may be useful to rule-in the possible diagnosis of CA in patients with unclear LV hypertrophy.

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Diagnosis of Cardiac Transthyretin Amyloidosis by Technetium-99m Pyrophosphate Heart Scan, Confirmed by Genetic Mutations: Case Report

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2021.11.13092 ◽

2021 ◽

Vol 104 (11) ◽

pp. 1843-1846

Keyword(s):

Heart Failure ◽

Case Report ◽

Genetic Testing ◽

Cardiac Amyloidosis ◽

Abdominal Fat ◽

Genetic Mutations ◽

Fat Pad ◽

Transthyretin Amyloidosis ◽

Technetium 99M ◽

Clinically Significant

Amyloid deposition in the myocardium can cause clinically significant heart failure, which is very difficult to diagnose. The present case reported presented a patient with heart failure, with suspected cause of cardiac amyloidosis, but abdominal fat pad and endomyocardial with Congo red stain biopsies were negative. Due to high suspicion of cardiac amyloidosis, a technetium-99m pyrophosphate (Tc-99m PYP) heart scan was done, which was revealed as strongly suggestive for cardiac transthyretin amyloidosis. So, the patient was sent for genetic testing, and a TTR gene mutation [c.148G>A (p.Val50Met)] was found. Keywords: Cardiac amyloidosis; Endomyocardial biopsy (EMB); Technetium-99m pyrophosphate (Tc-99m PYP) heart scan; Transthyretin amyloidosis (TTR)

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Relationship between CCR and NT-proBNP in Chinese HF Patients, and Their Correlations with Severity of HF

BioMed Research International ◽

10.1155/2014/106252 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Zhigang Lu ◽

Bo Wang ◽

Yunliang Wang ◽

Xueqing Qian ◽

Wei Zheng ◽

...

Keyword(s):

Heart Failure ◽

Smoking Status ◽

Characteristic Curve ◽

Heart Association ◽

Significant Negative Correlation ◽

Diagnostic Value ◽

Left Ventricular ◽

Chinese Patients ◽

Control Group ◽

Nyha Classification

Aim. To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity.Methods and Results. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value.Conclusion. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF.

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