Value of Longitudinal Strain to Identify Wild-Type Transthyretin Amyloidosis in Patients With Aortic Stenosis

Introduction: Both hereditary (hATTR) and wild-type (wtATTR) transthyretin amyloidosis are under-recognized causes of cardiomyopathy (CM) and heart failure. Certain findings on Transthoracic Echocardiography (TTE) and cardiac Magnetic Resonance Imaging (cMRI) are suggestive but not diagnostic of ATTR. Although biopsy historically has been the gold standard for diagnosis, patients can be diagnosed with the highly sensitive and specific technetium-99m pyrophosphate scan (Tc-99m PYP). Genetic testing is recommended to confirm hATTR in patients diagnosed with ATTR cardiac amyloidosis. Despite growing awareness of this condition, many cases remain undiagnosed. This study evaluated if patients with TTEs concerning for infiltrative CM received appropriate diagnostic testing for ATTR-CM. Methods: Our echocardiography registry was queried from January 2011 to March 2020 for patients with our echo lab’s embedded infiltrative CM code. Data on demographics, comorbidities, TTE variables, cMRI results, PYP scans, genetic testing and biopsy results were retrieved from electronic medical records. Thorough manual chart review excluded other causes of CM. Data was expressed as mean ± SD and n (%). Results: We retrieved 510 patients (mean age 64 ± 16 years; 43% female) with TTEs suspicious for infiltrative CM revealing a mean interventricular septal diameter (IVSd) of 1.6 ± 0.3 cm. Only 67 (13%) patients underwent cMRI with 11 (16%) suggestive of cardiac amyloidosis. Of the patients with suspicious TTEs, 16 (3.1%) had PYP scans and 24 (4.7%) had tissue biopsy, with positive results in 7 (44%) and 11 (46%), respectively. Genetic testing in 31 (6%) patients revealed known hATTR mutations in 2 (6.5%) patients. Cardiac amyloidosis was diagnosed in 23 (4.5%) with 11 ATTR (2 hATTR), 5 amyloid light chain, and 7 unknown subtype. Conclusion: Despite clinical and TTE findings suspicious for ATTR-CM, many patients did not undergo appropriate confirmatory testing (see Figure 1).

Download Full-text

Longitudinal strain assessed by cardiac magnetic resonance correlates to hemodynamic findings in patients with severe aortic stenosis and predicts positive remodeling after transcatheter aortic valve replacement

Clinical Research in Cardiology ◽

10.1007/s00392-017-1153-7 ◽

2017 ◽

Vol 107 (1) ◽

pp. 20-29 ◽

Cited By ~ 16

Author(s):

Dominik Buckert ◽

Maciej Cieslik ◽

Raid Tibi ◽

Michael Radermacher ◽

Volker Rasche ◽

...

Keyword(s):

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Aortic Valve ◽

Aortic Stenosis ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Transcatheter Aortic Valve Replacement ◽

Longitudinal Strain ◽

Severe Aortic Stenosis ◽

Transcatheter Aortic Valve

Download Full-text

Sex-related differences in the clinical characteristics of wild-type transthyretin amyloidosis cardiomyopathy

Journal of Cardiology ◽

10.1016/j.jjcc.2021.10.007 ◽

2021 ◽

Author(s):

Seiji Takashio ◽

Toshihiro Yamada ◽

Masato Nishi ◽

Mami Morioka ◽

Akira Fujiyama ◽

...

Keyword(s):

Clinical Characteristics ◽

Wild Type ◽

Transthyretin Amyloidosis

Download Full-text

Abstract 17246: Sensitivity and Specificity of Relative Sparing of Apical Longitudinal Strain for Detection of Systemic Light-Chain Amyloidosis versus Transthyretin Amyloidosis

Circulation ◽

10.1161/circ.142.suppl_3.17246 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Michael Jiang ◽

Julia M Simkowski ◽

Nadia El Hangouche ◽

Jeesoo Lee ◽

Milica Marion ◽

...

Keyword(s):

Left Ventricular Hypertrophy ◽

Sensitivity And Specificity ◽

Light Chain ◽

Longitudinal Strain ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Control Group ◽

Transthyretin Amyloidosis ◽

Light Chain Amyloidosis ◽

Significant Difference

Introduction: Relative apical sparing of longitudinal strain (RALS, the ratio of apical strain vs the rest of the heart) on echocardiography has been found to have high sensitivity and specificity for differentiating cardiac amyloidosis (CA) from other causes of left ventricular hypertrophy. Previous studies have shown no significant difference between amyloid subtypes, systemic light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) Hypothesis: There will be a significant difference in sensitivity and specificity of RALS to detect CA across amyloid subtypes. Methods: A cohort of patients with either AL or ATTR amyloid was identified, with a control cohort of patients with left ventricular hypertrophy (LVH) of other etiologies. Speckle tracking echocardiography was performed on EchoPAC (GE Medical Systems) software to obtain values of basal, mid, and apical longitudinal strain for each patient; relative apical strain was then calculated. Results: The TTR group (n=22) was older (66.4±7.9, 76.6±11.6, p=0.001) and more likely to be female (p=0.009) than the AL group (n=30), both groups had similar rates of hypertension, diabetes mellitus, and end stage renal disease. Echocardiographic markers of diastolic function were decreased in both groups; the AL group had decreased left ventricle end diastolic volume (60.9±25.5, 94.9±50.2, p=0.012) and mean wall thickness (1.4±0.3, 1.6±0.4 p=0.017). ROC analysis using a RALS cutoff of 2 to differentiate AL and ATTR from the LVH control group revealed similar specificity (AL 85%, ATTR 85%) and sensitivity (AL 40%, ATTR 50%). Difference in area-under-curve (AUC) was not significant (p=0.2) (figure). Conclusions: ATTR and AL amyloid have similar specificity, but ATTR has a trend towards improved sensitivity over AL for detection of CA using RALS with the previously validated threshold of 2. This might become significant with a larger sample, work that is currently on-going..

Download Full-text

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.

Download Full-text