Subclinical Cardiac Involvement in Asymptomatic ATTR Mutation Carriers: Insights from Cardiac MRI, Myocardial Strain, and Mapping Techniques

Figures

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  Figure 1. Diagnostic algorithm for patients with suspected ATTR-CA (A) and subjects with ATTR-MC (B). ATTR, Amyloid TransThyretin-Related; CA, Cardiac Amyloidosis; MC, Mutation Carriers; CMR, Cardiac Magnetic Resonance; sIFE, Serum Immunofixation Electrophoresis; uIFE, Urine Immunofixation Electrophoresis; 99mTc-PYP, Technetium PyroPhosphate.

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  Figure 2. Case Study: Comparison among Relatives. On the left are the CMR images of the son, 54 y, carrier of the mutation Ile88Leu of the TTR gene, with a preserved EF (55%) and a normal MWT (10 mm) in the cine images (A), a mildly impaired GLS in the strain analysis (−16.1 ± 4.3%, (B,C)), no LGE (D,E) and normal nT1 values (1235 ± 40; normal range: 1153–1307 ms, (F)). On the right are the CMR images of the Father, 77 y, with CA related to the same mutation, with a reduced EF (35%), a moderate LV hypertrophy (18 mm) in the cine images (G), a severely impaired GLS in the strain analysis (−9 ± 5.9%, (H,I)), typical LGE pattern (J,K) and incremented nT1 values (1435 ± 30, (L)). ATTR, Amyloid TransThyretin Related; MC, Mutation Carrier; Ile, Ileleucin; Leu, Leucine; CA, Cardiac Amyloidosis; CMR, Cardiac Magnetic Resonance; TTR, TransThyretin; EF, Ejection Fraction; MWT, Maximum Wall Thickness; LGE, Late Gadolinium Enhancement; nT1, Native T1.

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  Figure 3. Graphical representation of the distribution of ATTR mutations in the study population: (A) in patients with ATTR-CA and (B) in subjects with ATTR-MC. ATTR, Amyloid TransThyretin Related; CA, Cardiac Amyloidosis; MC, Mutation Carriers; ILE, Ileleucin; Leu, Leucine; Phe, phenylalanine; Val, Valine; Met, Methionine.

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  Figure 4. Box plot representation of the ANOVA comparison of nT1 (A) and ECV (B) among ATTR-CA, ATTR-MC, and Controls groups. ATTR, Amyloid TransThyretin Related; CA, Cardiac Amyloidosis; MC, Mutation Carriers; nT1, Native; ECV, ExtraCellular Volume.

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  Figure 5. Box plot representation of the ANOVA comparison of LV strain parameters—specifically GLS (A) and GCS (B)—among ATTR-CA, ATTR-MC, and HC groups. LV, Left Ventricle; ATTR, Amyloid TransThyretin Related; CA, Cardiac Amyloidosis; MC, Mutation Carriers; C, Controls; GLS, Global Longitudinal Strain; GCS, Global Circumferential Strain.

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  Figure 6. Graphical representation of the ANOVA comparison of LV strain parameters—specifically GLS (A) and GCS (B)—among ATTR-CA, ATTR-MC, and HC groups. LV, Left Ventricle; ATTR, Amyloid TransThyretin Related; CA, Cardiac Amyloidosis; MC, Mutation Carriers; C, Controls; GLS, Global Longitudinal Strain; GCS, Global Circumferential Strain.

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  Figure 7. Box plot representation of the ANOVA comparison of LA strain parameters—specifically RS (A), CS (B), and BPS (C)—among ATTR-CA, ATTR-MC, and HC groups. LA, Left Atrial; ATTR, Amyloid TransThyretin Related; CA, Cardiac Amyloidosis; MC, Mutation Carriers; C, Controls; RS, Reservoir Strain; CS, Conduit Strain; BPS, Booster Pump Strain.

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  Figure 8. ROC Curves for Diagnostic Accuracy of LV/LA strain parameters and nT1/ECV values between ATTR-MC and Controls. Each curve is annotated with the corresponding AUC value, showcasing the performance of each parameter. Optimal thresholds for sensitivity and specificity were determined using Youden’s index. ROC, Receiver Operating Characteristic; ATTR, Amyloid TransThiretin related; MC, Mutation Carriers; HC, Healthy Controls; LV, Left Ventricle; LA, Left Atrium; GLS, Global Longitudinal Strain; GCS, Global Circumferential Strain; RS, Reservoir Strain; CS, Conduit Strain; BPS, Booster Pump Strain; nT1, native T1; ECV, ExtraCellular Volume; AUC, Area Under the Curve.