Left Ventricular Deformation and Myocardial Work Parameters in Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran: A Single-Center Study
Abstract
:1. Introduction
2. Materials and Methods
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- Age ≥ 18 years old;
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- Hereditary transthyretin amyloidosis with polyneuropathy with or without cardiomyopathy;
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- Signed informed consent for participation in this study.
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- Other forms of non-amyloidotic heart disease;
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- Non-mutational transthyretin-related cardiac amyloidosis;
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- Other forms of non-amyloidotic neuropathy;
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- Patients carrying a mutation in the gene encoding transthyretin without clinical manifestations (cardiac and/or neurological);
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- Multiple myeloma and/or other cancer.
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- Hereditary transthyretin amyloid cardiomyopathy with neuropathy: Group A;
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- Hereditary transthyretin amyloidosis with only neuropathy: Group B.
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- Cardiology examination with comprehensive medical history collection assessing the presence of cardiovascular risk factors (arterial hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, obesity) and cardiovascular comorbidities (including ischemic heart disease, peripheral artery diseases, transient ischemic attacks, and strokes); measurement of blood pressure and recording of main anthropometric/functional variables (weight, height, BMI, BSA, NYHA);
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- ECG (electrocardiogram) with assessment of rhythm, atrial abnormalities, atrioventricular and intraventricular conduction anomalies (atrioventricular blocks, bundle branch blocks, and hemiblocks), pseudonecrosis waves, arrhythmias (e.g., atrial fibrillation);
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- Laboratory test with complete blood count, urea, creatinine, potassium, sodium, c-TnT-hs (high-sensitivity cardiac troponin T), AST (aspartate aminotransferase), ALT (alanine aminotransferase), total cholesterol, HDL (high-density lipoprotein), LDL (calculated by the Friedewald formula), triglycerides, blood glucose, and NT-proBNP (N-terminal pro-B-type natriuretic peptide);
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- Color-Doppler echocardiography with assessment of conventional echocardiographic parameters and myocardial deformation indices of the left ventricle and left atrium; assessment of myocardial work parameters;
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- Bone scintigraphy with diphosphonates assessing cardiac uptake according to the Perugini scale;
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- Cardiac magnetic resonance imaging with and without contrast agent, evaluating T1-T2 mapping and extracellular volume (ECV);
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- Six-minute walk test to assess functional capacity;
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- Assessment of quality of life was conducted through the completion of the Kansas City Cardiomyopathy Questionnaire (KCCQ);
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- Neurological evaluation, including a comprehensive general neurological examination (tests to assess muscle strength, reflexes, sensitivity, and coordination), electromyography, and electroneurography to evaluate peripheral nervous system function and integrity, along with assessment of cognitive and sensory functions (memory, attention, language, and other cognitive functions, as well as sensory sensitivity).
2.1. Echocardiography Evaluation
2.2. Statistical Analysis
3. Results
3.1. Results Pre- and Post Treatment with Patisiran in Neuropathic Patients
3.2. Results Pre- and Post Treatment with Patisiran in Patients with Cardiomyopathy
4. Discussion
5. Conclusions
6. Study Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Features | Value | |
---|---|---|
Sex n° pts (%) | Male | 11 (52%) |
Female | 10 (48%) | |
Age (mean y.o. ± DS) | 66 ± 8 | |
BMI (mean Kg/mq ± DS) | 26 ± 7 | |
Arterial hypertension | 9 (42.9%) | |
Cardiovascular risk factors n° patients (%) | Diabetes mellitus | 1 (4.8%) |
Dyslipidemia | 10 (47%) | |
Smoking | 3 (14%) | |
Family history of CVD | 6 (28%) | |
Other CV comorbidities | 5 (24%) | |
Therapy n° patients (%) | Beta-blocker | 9 (42.9%) |
Calcium channel blocker | 4 (19%) | |
ACE-i/ARB | 5 (23%) | |
Antiplatelet agent | 7 (33%) | |
Diuretic | 3 (14%) | |
Statins | 7 (33%) | |
Ezetimibe | 1 (4.8%) | |
Patisiran | 17 (80.95%) | |
Tafamidis | 3 (14.29%) |
Features | Cardiac Amyloidosis (7 Pts) | Neuropathy (14 pts) | p-Value |
---|---|---|---|
Male n° patients (%) | 7 (100%) | 4 (29%) | 0.0027 |
Female n° patients (%) | 0 (0%) | 10 (71%) | 0.0027 |
Age (value ± DS) | 66 ± 8.4 | 65.7 ± 7.8 | 0.93 |
BMI (Kg/mq) | 26 ± 5.6 | 26 ± 7.4 | 1 |
Hypertension n° patients (%) | 3 (42.86%) | 6 (46%) | 0.89 |
Diabetes mellitus n° patients (%) | 0 (0%) | 1 (7.69%) | 0.46 |
Dyslipidemia n° patients (%) | 2 (28.5%) | 7 (53.8%) | 0.28 |
Smoking n° patients (%) | 1 (14.29%) | 2 (15.38%) | 0.94 |
Family history of CVD n° patients (%) | 1 (14.29%) | 5 (38.5%) | 0.26 |
Other cardiovascular comorbidities n° patients (%) | 1 (14.29%) | 4 (30.7%) | 0.42 |
Echocardiographic Parameters | Neuropathy T0 | Neuropathy T1 (p-Value) | Neuropathy T2 (p-Value) |
---|---|---|---|
IVS (mm) | 10.21 ± 2.12 | 10.69 ± 1.84 (0.52) | 11 ± 2 (0.31) |
PW (mm) | 8.86 ± 1.83 | 9.54 ± 1.61 (0.30) | 10 ± 1 (0.051) |
LVEF 2D (%) | 60.14 ± 5.25 | 59.23 ± 4.95 (0.64) | 57 ± 4 (0.08) |
End diastolic volume (mL/mq) | 77.5 ± 20.3 | 80.23 ± 23.34 (0.74) | 89 ± 29 (0.23) |
S’ septal (cm/s) | 9.33 ± 2.99 | 8 ± 1.8 (0.16) | 8 ± 3 (0.25) |
S’ lateral (cm/s) | 10.67 ± 3.08 | 8.62 ± 2.60 (0.06) | 9 ± 4 (0.22) |
E/e’ mean | 8.22 ± 3.89 | 9.52 ± 4 (0.35) | 11 ± 7 (0.19) |
TAPSE (mm) | 22.31 ± 4 | 20.62 ± 1.8 (0.16) | 21 ± 3 (0.33) |
LA vol Biplane (mL) | 58.93 ± 25.10 | 62.69 ± 21.76 (0.67) | 64 ± 14 (0.51) |
GLS LV 2D (%) | −20.40 ± 3.57 | −19.69 ± 3.81 (0.61) | −19.88 ± 2.69 (0.66) |
PALS (%) | 24.65 ± 11.35 | 25.21 ± 1.36 (0.85) | 20 ± 5 (0.17) |
Atrial Stiffness | 0.45 ± 0.43 | 0.56 ± 0.51 (0.54) | 0.54 ± 0.5 (0.61) |
GWI (mmHg%) | 1911 ± 408 | 1830 ± 402 (0.60) | 1800 ± 145 (0.34) |
GCW (mmHg%) | 2293 ± 474 | 2168 ± 462 (0.48) | 2100 ± 162 (0.16) |
GWW (mmHg%) | 78.33 ± 47.51 | 109.18 ± 79.85 (0.22) | 68 ± 40 (0.53) |
GWE (%) | 95.78 ± 2.05 | 94.45 ± 2.46 (0.12) | 95 ± 2 (0.31) |
SAB ratio | 1.58 ± 0.27 | 1.68 ± 0.62 (0.58) | 1.76 ± 0.22 (0.06) |
Relative apical sparing | 0.71 ± 0.09 | 0.70 ± 0.17 (0.84) | 0.88 ± 0.2 (0.0075) |
NT-proBNP (pg/mL) | 264 ± 401 | 183 ± 200 (0.5) | 269 ± 300 (0.97) |
Hs TnT (ng/L) | 4.47 ± 5.4 | 1.6 ± 3 (0.09) | 1.5 ± 1.7 (0.06) |
Echocardiographic Parameters | Cardiac Amyloidosis T0 | Cardiac Amyloidosis T1 (p-Value) | Cardiac Amyloidosis T2 (p-Value) |
---|---|---|---|
IVS (mm) | 17 ± 4 | 17.25 ± 3.30 (0.85) | 17 ± 3 (1) |
PW (mm) | 15 ± 3 | 14.5 ± 2.08 (0.72) | 15 ± 2 (1) |
LVEF 2D (%) | 52 ± 7 | 52 ± 3.56 (1) | 52 ± 4 (1) |
End diastolic volume (mL/mq) | 93 ± 29 | 106 ± 18 (0.33) | 104 ± 24 (0.45) |
S’ septal (cm/s) | 81 ± 25 | 97.2 ± 20 (0.21) | 94 ± 21 (0.31) |
S’ lateral (cm/s) | 5 ± 2 | 4.75 ± 0.96 (0.77) | 6 ± 1 (0.25) |
E/e’ mean | 7 ± 2 | 6.5 ± 1 (0.56) | 7 ± 1 (1) |
TAPSE (mm) | 15 ± 5 | 10.3 ± 3 (0.05) | 10.2 ± 2.5 (0.04) |
LA vol Biplane (mL) | 18 ± 6 | 20.5 ± 4.6 (0.39) | 20 ± 4 (0.47) |
GLS LV 2D (%) | −13 ± 5 | −14.6 ± 2.36 (0.45) | −17.2 ± 1.29 (0.05) |
PALS (%) | 12 ± 6 | 12.89 ± 5 (0.76) | 12 ± 4 (1) |
Atrial Stiffness | 2 ± 1 | 1 ± 0.66 (0.04) | 1 ± 0.6 (0.04) |
GWI (mmHg%) | 1247 ± 591 | 1372 ± 423 (0.65) | 1383 ± 193 (0.57) |
GCW (mmHg%) | 1483 ± 619 | 1565 ± 371 (0.76) | 1629 ± 204 (0.56) |
GWW (mmHg%) | 162 ± 95 | 76 ± 35 (0.04) | 64 ± 8 (0.01) |
GWE (%) | 88 ± 6 | 91 ± 1.71 (0.22) | 94 ± 2 (0.02) |
SAB ratio | 3.3 ± 2.1 | 2.59 ± 1.37 (0.4) | 2.17 ± 1 (0.22) |
Relative apical sparing | 1.3 ± 0.6 | 1.03 ± 0.41 (0.34) | 1.02 ± 0.35 (0.30) |
NT-proBNP (pg/mL) | 1956 ± 3297 | 860 ± 1198 (0.42) | 764 ± 453 (0.36) |
Hs TnT (ng/L) | 31 ± 48 | 29 ± 10 (0.91) | 27 ± 9 (0.83) |
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Di Lisi, D.; Comparato, F.; Ortello, A.; Di Stefano, V.; Brighina, F.; Macaione, F.; La Fiura, G.; Di Caccamo, L.; Madaudo, C.; Galassi, A.R.; et al. Left Ventricular Deformation and Myocardial Work Parameters in Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran: A Single-Center Study. J. Clin. Med. 2024, 13, 4914. https://doi.org/10.3390/jcm13164914
Di Lisi D, Comparato F, Ortello A, Di Stefano V, Brighina F, Macaione F, La Fiura G, Di Caccamo L, Madaudo C, Galassi AR, et al. Left Ventricular Deformation and Myocardial Work Parameters in Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran: A Single-Center Study. Journal of Clinical Medicine. 2024; 13(16):4914. https://doi.org/10.3390/jcm13164914
Chicago/Turabian StyleDi Lisi, Daniela, Francesco Comparato, Antonella Ortello, Vincenzo Di Stefano, Filippo Brighina, Francesca Macaione, Giovanni La Fiura, Leandro Di Caccamo, Cristina Madaudo, Alfredo R. Galassi, and et al. 2024. "Left Ventricular Deformation and Myocardial Work Parameters in Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran: A Single-Center Study" Journal of Clinical Medicine 13, no. 16: 4914. https://doi.org/10.3390/jcm13164914