https://orcid.org/0000-0002-0452-4384
Abstract
Although tafamidis is used in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), its specific effect on cardiac function is unclear. Thus, this study aimed to investigate the effect of tafamidis on left atrial (LA) and left ventricular function using speckle-tracking echocardiography for 1 year of treatment in patients with ATTRwt-CA.
We included 23 patients (mean age, 76 years) with ATTRwt-CA confirmed via biopsy. We analysed the left ventricular and LA strain using 2D speckle-tracking echocardiography and compared these parameters before and 1 year after starting treatment with tafamidis between 16 patients with sinus rhythm (SR) and 7 patients with atrial fibrillation (AF). In ATTRwt-CA patients with SR, LA reservoir strain significantly improved by 1-year tafamidis treatment (10.5 ± 5.0% to 11.9 ± 5.3%, P = 0.0307) although global longitudinal strain (GLS) did not (−10.6 ± 3.1% to −11.3 ± 3.0%, P = 0.0608). In contrast, LA reservoir strain was not significantly changed (5.4 ± 2.9% to 4.9 ± 1.7%, P = 0.4571), and GLS deteriorated (−8.4 ± 2.3% to −6.8 ± 1.4%, P = 0.0267) in ATTRwt-CA patients with AF.
LA function improved with tafamidis treatment in ATTRwt-CA patients with SR but not left ventricular function. However, these cardiac functions did not improve with tafamidis treatment in ATTRwt-CA patients with AF.
Introduction
Cardiac amyloidosis (CA) is a progressive disease caused by the deposition of amyloid fibrils in the myocardium.1 It involves the atria, ventricles, and conduction system.2 Light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis are the most common types of CA in clinical practice.1
Tafamidis is available for ATTR-CA because it reduces all-cause mortality and cardiovascular hospitalization in patients with ATTR-CA compared with placebo.3–6
Global longitudinal strain (GLS), assessed using 2D speckle-tracking echocardiography (2D-STE), is a sensitive marker for earlier abnormalities in left ventricular (LV) myocardial function than in LV ejection fraction.7 Recently, 2D-STE has been shown to be useful for quantitative assessment of left atrial (LA) function.
Few studies have evaluated the effectiveness of tafamidis in ATTR-CA using echocardiography.8–11
Atrial fibrillation (AF) is commonly encountered in ATTR.12,13 ATTR-CA includes significant infiltration of the atrial walls with progressive loss of atrial function and increased stiffness, which are strong independent predictors of mortality.14
However, the specific effects of tafamidis on atrial and ventricular function and between AF and sinus rhythm (SR) have not been recognized.
This study aimed to evaluate the effect of 1-year treatment on atrial and ventricular functions in AF and SR using 2D-STE in patients with wild-type ATTR-CA (ATTRwt-CA).
Methods
Study population
We retrospectively studied 37 consecutive patients with ATTRwt-CA who were treated with tafamidis and followed up for 1 year at the Nagasaki University Hospital between December 2019 and July 2023. In all patients, TTR was confirmed by cardiac or extracardiac biopsy, and genetic examination for TTR showed no variants.
Cardiac devices affect LA function; hence, six patients were excluded from this study: three patients with a dual-chamber pacemaker, one patient with a single-chamber (VVI) pacemaker, and two patients with implantable cardiac resynchronization therapy. Additionally, three patients for post-mitral valve replacement and another three patients who underwent catheter ablation treatment for AF were excluded. Two patients were further excluded because of poor visualization on transthoracic echocardiography. Finally, 23 patients were included in this study (Figure 1).
Study flow chart of this study. ATTR, transthyretin; CTR-D, cardiac resynchronization therapy defibrillator.
This study was approved by the Ethics Committee of Nagasaki University Hospital (23022013) and conducted in accordance with the Declaration of Helsinki.
Standard echocardiographic assessment
Echocardiography was performed using the GE Vivid E95 system version 203, and images were acquired from standard views. Cardiac function was assessed using transthoracic echocardiography before and 1 year after tafamidis treatment. All standard echocardiographic measurements were performed in accordance with the European Association of Cardiovascular Imaging guidelines.
Speckle-tracking LV and LA analysis
Speckle-tracking analysis was performed offline using a software package (EchoPAC, General Electric version 204) to evaluate LV GLS and LA strain (LAS).
Global longitudinal strain
For GLS deformation analysis, the longitudinal strain was calculated using an automated contouring detection algorithm. The averaged peak longitudinal strain of 17 segments from apical four-, two-, and three-chamber views was generated as a ‘bull’s-eye’ map (Figure 2A).
Echocardiographic global longitudinal and LAS. (A) GLS imaging examples before and 1 year after tafamidis treatment in patients with wild-type transthyretin CA with SR. (B) LAS imaging examples before and 1 year after tafamidis treatment in patients with wild-type transthyretin CA with SR. GLS, global longitudinal strain; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain.
LA strain
Phasic LAS was analysed using a standard 2D apical four-chamber view (offline analysis, EchoPAC, GE). The LAS was measured, including LA reservoir strain (LASr), conduit strain (LAScd), and contractile strain (LASct), according to the recommendation of the consensus document of the European Association of Cardiovascular Imaging/American Society of Echocardiography/industry using a non-foreshortened apical four-chamber view of the left atrium (Figure 2B). The region of interest was adjusted to a 3 mm full wall or an endocardial contouring tool. The LA was contoured by extrapolation across the pulmonary veins and LA appendage orifice. An average of three measurements was used in the final analysis of strain based on the committee’s suggestion in patients with normal SR and a minimum of five beats in patients with AF.
Inter-observer variability
All analyses were performed by a single experienced physician. To ensure reproducibility, GLS and LAS were re-measured in a random sample of 10 anonymized studies by another experienced operator blinded to the treatment and echo timing to determine inter-observer variability using an interclass correlation coefficient (ICC).
Statistical analysis
Baseline characteristics are summarized as median and interquartile range for continuous variables and counts (%) for categorical variables. Characteristics between the two groups (SR group and AF group) were compared using the Wilcoxon rank-sum test or Fisher’s exact test, as appropriate.
Parameters at baseline and 1 year after treatment were compared using a paired t-test or Wilcoxon signed-rank test, as appropriate.
All hypothesis tests were two sided, and statistical significance was set at P < 0.05. All analyses were performed using the JMP statistical software (JMP 17Pro, SAS Institute, Cary, NC, USA).
Results
No significant difference was found in baseline clinical and laboratory data characteristics between patients with SR and those with AF (Table 1). Regarding baseline echocardiographic parameters, LAD and LAVI were smaller and LASr and LASct were larger in the SR group than in the AF group (Table 2).
Baseline clinical and laboratory data characteristics
| Characteristics | All | SR | AF | P-values (AF vs. SR) |
|---|---|---|---|---|
| n = 23 | n = 16 | n = 7 | ||
| Age (years) | 76 ± 5 | 76 ± 5 | 76 ± 6 | 0.8667 |
| Male, n (%) | 23 (100) | 16 (100) | 7 (100) | 1.0000 |
| Hypertension, n (%) | 17 (74) | 12 (75) | 5 (71) | 1.0000 |
| Diabetes Mellitus, n (%) | 8 (34) | 4 (25) | 4 (57) | 0.1819 |
| Dyslipidaemia, n (%) | 6 (26) | 5 (31) | 1 (14) | 0.6214 |
| Obesity, n (%) | 4 (17) | 4 (25) | 0 (0) | 0.2727 |
| BMI (kg/m2) | 22.6 ± 2.5 | 22.8 ± 6 | 22.2 ± 1.6 | 0.5034 |
| NYHA class II, n (%) | 15 (65) | 12 (75) | 3 (43) | 0.1819 |
| NYHA class III, n (%) | 8 (35) | 4 (25) | 4 (57) | 0.1819 |
| SBP (mmHg) | 118 ± 20 | 124 ± 20 | 106 ± 14 | 0.0817 |
| DBP (mmHg) | 73 ± 14 | 76 ± 14 | 67 ± 11 | 0.1238 |
| Heart rate (/min) | 69 ± 9 | 67 ± 9 | 74 ± 8 | 0.0944 |
| Hb (g/dL) | 13.8 ± 1.2 | 14.3 ± 1.3 | 13.8 ± 1.2 | 0.4824 |
| eGFR (mL/min/1.73m2) | 46 ± 14 | 48 ± 11 | 43 ± 19 | 0.1923 |
| AST (IU/L) | 24 (19–27) | 24 (19–27) | 23 (17–31) | 0.9466 |
| ALT (IU/L) | 17 (10–19) | 17 (11–20) | 12 (9–18) | 0.2538 |
| CK (IU/L) | 94 (68–160) | 98 (70–167) | 71 (40–156) | 0.2421 |
| Hs-TnT (ng/mL) | 0.064 (0.042–0.099) | 0.062 (0.039–0.094) | 0.066 (0.053–0.105) | 0.4828 |
| LDL-C (mg/dL) | 92 ± 31 | 90 ± 30 | 99 ± 33 | 0.5697 |
| NT-proBNP (pg/mL) | 1898 (832–3291) | 1697 (762–1981) | 3533 (2284–7168) | 0.0177 |
| ACEi/ARB, n (%) | 11 (58) | 7 (48) | 4 (57) | 0.6668 |
| Beta blocker, n (%) | 15 (65) | 8 (50) | 7 (100) | 0.0520 |
| MRA, n (%) | 8 (34) | 6 (38) | 2 (29) | 1.0000 |
| Diuretics, n (%) | 11 (48) | 6 (38) | 5 (71) | 0.1930 |
| ARNI, n (%) | 2 (9) | 2 (13) | 0 (0) | 1.0000 |
| SGLT2I, n (%) | 5 (22) | 4 (25) | 1 (14) | 1.0000 |
| CCB, n (%) | 3 (13) | 0 (0) | 3 (19) | 0.5257 |
| Characteristics | All | SR | AF | P-values (AF vs. SR) |
|---|---|---|---|---|
| n = 23 | n = 16 | n = 7 | ||
| Age (years) | 76 ± 5 | 76 ± 5 | 76 ± 6 | 0.8667 |
| Male, n (%) | 23 (100) | 16 (100) | 7 (100) | 1.0000 |
| Hypertension, n (%) | 17 (74) | 12 (75) | 5 (71) | 1.0000 |
| Diabetes Mellitus, n (%) | 8 (34) | 4 (25) | 4 (57) | 0.1819 |
| Dyslipidaemia, n (%) | 6 (26) | 5 (31) | 1 (14) | 0.6214 |
| Obesity, n (%) | 4 (17) | 4 (25) | 0 (0) | 0.2727 |
| BMI (kg/m2) | 22.6 ± 2.5 | 22.8 ± 6 | 22.2 ± 1.6 | 0.5034 |
| NYHA class II, n (%) | 15 (65) | 12 (75) | 3 (43) | 0.1819 |
| NYHA class III, n (%) | 8 (35) | 4 (25) | 4 (57) | 0.1819 |
| SBP (mmHg) | 118 ± 20 | 124 ± 20 | 106 ± 14 | 0.0817 |
| DBP (mmHg) | 73 ± 14 | 76 ± 14 | 67 ± 11 | 0.1238 |
| Heart rate (/min) | 69 ± 9 | 67 ± 9 | 74 ± 8 | 0.0944 |
| Hb (g/dL) | 13.8 ± 1.2 | 14.3 ± 1.3 | 13.8 ± 1.2 | 0.4824 |
| eGFR (mL/min/1.73m2) | 46 ± 14 | 48 ± 11 | 43 ± 19 | 0.1923 |
| AST (IU/L) | 24 (19–27) | 24 (19–27) | 23 (17–31) | 0.9466 |
| ALT (IU/L) | 17 (10–19) | 17 (11–20) | 12 (9–18) | 0.2538 |
| CK (IU/L) | 94 (68–160) | 98 (70–167) | 71 (40–156) | 0.2421 |
| Hs-TnT (ng/mL) | 0.064 (0.042–0.099) | 0.062 (0.039–0.094) | 0.066 (0.053–0.105) | 0.4828 |
| LDL-C (mg/dL) | 92 ± 31 | 90 ± 30 | 99 ± 33 | 0.5697 |
| NT-proBNP (pg/mL) | 1898 (832–3291) | 1697 (762–1981) | 3533 (2284–7168) | 0.0177 |
| ACEi/ARB, n (%) | 11 (58) | 7 (48) | 4 (57) | 0.6668 |
| Beta blocker, n (%) | 15 (65) | 8 (50) | 7 (100) | 0.0520 |
| MRA, n (%) | 8 (34) | 6 (38) | 2 (29) | 1.0000 |
| Diuretics, n (%) | 11 (48) | 6 (38) | 5 (71) | 0.1930 |
| ARNI, n (%) | 2 (9) | 2 (13) | 0 (0) | 1.0000 |
| SGLT2I, n (%) | 5 (22) | 4 (25) | 1 (14) | 1.0000 |
| CCB, n (%) | 3 (13) | 0 (0) | 3 (19) | 0.5257 |
ACEI, angiotensin-converting enzyme inhibitor; ALT, alanine aminotransferase; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; AST, aspartate aminotransferase; BMI, body mass index; CCB, calcium channel blocker; CK, creatine kinase; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; Hb, haemoglobin; Hs-TnT, high-sensitivity troponin T; LDL-C, low-density lipoprotein cholesterol; MRA, mineralocorticoid receptor antagonist; NT-proBNP, N-terminal pro–B-type natriuretic peptide; NYHA, New York Heart Association; SBP, systolic blood pressure; SGLT2, sodium-glucose co-transporter 2.
Baseline clinical and laboratory data characteristics
| Characteristics | All | SR | AF | P-values (AF vs. SR) |
|---|---|---|---|---|
| n = 23 | n = 16 | n = 7 | ||
| Age (years) | 76 ± 5 | 76 ± 5 | 76 ± 6 | 0.8667 |
| Male, n (%) | 23 (100) | 16 (100) | 7 (100) | 1.0000 |
| Hypertension, n (%) | 17 (74) | 12 (75) | 5 (71) | 1.0000 |
| Diabetes Mellitus, n (%) | 8 (34) | 4 (25) | 4 (57) | 0.1819 |
| Dyslipidaemia, n (%) | 6 (26) | 5 (31) | 1 (14) | 0.6214 |
| Obesity, n (%) | 4 (17) | 4 (25) | 0 (0) | 0.2727 |
| BMI (kg/m2) | 22.6 ± 2.5 | 22.8 ± 6 | 22.2 ± 1.6 | 0.5034 |
| NYHA class II, n (%) | 15 (65) | 12 (75) | 3 (43) | 0.1819 |
| NYHA class III, n (%) | 8 (35) | 4 (25) | 4 (57) | 0.1819 |
| SBP (mmHg) | 118 ± 20 | 124 ± 20 | 106 ± 14 | 0.0817 |
| DBP (mmHg) | 73 ± 14 | 76 ± 14 | 67 ± 11 | 0.1238 |
| Heart rate (/min) | 69 ± 9 | 67 ± 9 | 74 ± 8 | 0.0944 |
| Hb (g/dL) | 13.8 ± 1.2 | 14.3 ± 1.3 | 13.8 ± 1.2 | 0.4824 |
| eGFR (mL/min/1.73m2) | 46 ± 14 | 48 ± 11 | 43 ± 19 | 0.1923 |
| AST (IU/L) | 24 (19–27) | 24 (19–27) | 23 (17–31) | 0.9466 |
| ALT (IU/L) | 17 (10–19) | 17 (11–20) | 12 (9–18) | 0.2538 |
| CK (IU/L) | 94 (68–160) | 98 (70–167) | 71 (40–156) | 0.2421 |
| Hs-TnT (ng/mL) | 0.064 (0.042–0.099) | 0.062 (0.039–0.094) | 0.066 (0.053–0.105) | 0.4828 |
| LDL-C (mg/dL) | 92 ± 31 | 90 ± 30 | 99 ± 33 | 0.5697 |
| NT-proBNP (pg/mL) | 1898 (832–3291) | 1697 (762–1981) | 3533 (2284–7168) | 0.0177 |
| ACEi/ARB, n (%) | 11 (58) | 7 (48) | 4 (57) | 0.6668 |
| Beta blocker, n (%) | 15 (65) | 8 (50) | 7 (100) | 0.0520 |
| MRA, n (%) | 8 (34) | 6 (38) | 2 (29) | 1.0000 |
| Diuretics, n (%) | 11 (48) | 6 (38) | 5 (71) | 0.1930 |
| ARNI, n (%) | 2 (9) | 2 (13) | 0 (0) | 1.0000 |
| SGLT2I, n (%) | 5 (22) | 4 (25) | 1 (14) | 1.0000 |
| CCB, n (%) | 3 (13) | 0 (0) | 3 (19) | 0.5257 |
| Characteristics | All | SR | AF | P-values (AF vs. SR) |
|---|---|---|---|---|
| n = 23 | n = 16 | n = 7 | ||
| Age (years) | 76 ± 5 | 76 ± 5 | 76 ± 6 | 0.8667 |
| Male, n (%) | 23 (100) | 16 (100) | 7 (100) | 1.0000 |
| Hypertension, n (%) | 17 (74) | 12 (75) | 5 (71) | 1.0000 |
| Diabetes Mellitus, n (%) | 8 (34) | 4 (25) | 4 (57) | 0.1819 |
| Dyslipidaemia, n (%) | 6 (26) | 5 (31) | 1 (14) | 0.6214 |
| Obesity, n (%) | 4 (17) | 4 (25) | 0 (0) | 0.2727 |
| BMI (kg/m2) | 22.6 ± 2.5 | 22.8 ± 6 | 22.2 ± 1.6 | 0.5034 |
| NYHA class II, n (%) | 15 (65) | 12 (75) | 3 (43) | 0.1819 |
| NYHA class III, n (%) | 8 (35) | 4 (25) | 4 (57) | 0.1819 |
| SBP (mmHg) | 118 ± 20 | 124 ± 20 | 106 ± 14 | 0.0817 |
| DBP (mmHg) | 73 ± 14 | 76 ± 14 | 67 ± 11 | 0.1238 |
| Heart rate (/min) | 69 ± 9 | 67 ± 9 | 74 ± 8 | 0.0944 |
| Hb (g/dL) | 13.8 ± 1.2 | 14.3 ± 1.3 | 13.8 ± 1.2 | 0.4824 |
| eGFR (mL/min/1.73m2) | 46 ± 14 | 48 ± 11 | 43 ± 19 | 0.1923 |
| AST (IU/L) | 24 (19–27) | 24 (19–27) | 23 (17–31) | 0.9466 |
| ALT (IU/L) | 17 (10–19) | 17 (11–20) | 12 (9–18) | 0.2538 |
| CK (IU/L) | 94 (68–160) | 98 (70–167) | 71 (40–156) | 0.2421 |
| Hs-TnT (ng/mL) | 0.064 (0.042–0.099) | 0.062 (0.039–0.094) | 0.066 (0.053–0.105) | 0.4828 |
| LDL-C (mg/dL) | 92 ± 31 | 90 ± 30 | 99 ± 33 | 0.5697 |
| NT-proBNP (pg/mL) | 1898 (832–3291) | 1697 (762–1981) | 3533 (2284–7168) | 0.0177 |
| ACEi/ARB, n (%) | 11 (58) | 7 (48) | 4 (57) | 0.6668 |
| Beta blocker, n (%) | 15 (65) | 8 (50) | 7 (100) | 0.0520 |
| MRA, n (%) | 8 (34) | 6 (38) | 2 (29) | 1.0000 |
| Diuretics, n (%) | 11 (48) | 6 (38) | 5 (71) | 0.1930 |
| ARNI, n (%) | 2 (9) | 2 (13) | 0 (0) | 1.0000 |
| SGLT2I, n (%) | 5 (22) | 4 (25) | 1 (14) | 1.0000 |
| CCB, n (%) | 3 (13) | 0 (0) | 3 (19) | 0.5257 |
ACEI, angiotensin-converting enzyme inhibitor; ALT, alanine aminotransferase; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; AST, aspartate aminotransferase; BMI, body mass index; CCB, calcium channel blocker; CK, creatine kinase; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; Hb, haemoglobin; Hs-TnT, high-sensitivity troponin T; LDL-C, low-density lipoprotein cholesterol; MRA, mineralocorticoid receptor antagonist; NT-proBNP, N-terminal pro–B-type natriuretic peptide; NYHA, New York Heart Association; SBP, systolic blood pressure; SGLT2, sodium-glucose co-transporter 2.
Baseline echocardiographic parameters
| SR (n = 16) | AF (n = 7) | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.3 ± 5.1 | 0.8932 |
| LVESD (mm) | 31.3 ± 3.5 | 35.6 ± 6.8 | 0.1395 |
| IVS (mm) | 15.3 ± 2.5 | 15.3 ± 2.9 | 0.9731 |
| PW (mm) | 14.6 ± 3.0 | 15.3 ± 2.5 | 0.6361 |
| LVEF (%) | 54.9 ± 9.0 | 47.3 ± 14.8 | 0.0818 |
| LAD (mm) | 42.0 ± 3.7 | 46.9 ± 4.6 | 0.0292 |
| LA area (cm2) | 23.3 ± 3.8 | 27.6 ± 5.9 | 0.0606 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 57.6 ± 16.2 | 0.0381 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 71.6 ± 18.4 | 0.3152 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 5.2 ± 1.0 | 0.8409 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.8 ± 0.9 | 0.7380 |
| Average E/E′ | 18.0 ± 6.5 | 16.9 ± 5.0 | 0.8411 |
| DT (ms) | 200.5 (165.25–239) | 177.6 ± 35.3 | 0.3003 |
| Speckle-tracking measurement | |||
| GLS (%) | −10.6 ± 3.1 | −8.4 ± 2.3 | 0.1414 |
| GLS 4ch (%) | −10.0 ± 3.3 | −7.7 ± 1.8 | 0.0947 |
| GLS 2ch (%) | −11.4 ± 3.2 | −8.7 ± 2.8 | 0.0945 |
| GLS apex (%) | −10.6 ± 3.2 | −8.7 ± 2.3 | 0.2164 |
| LASr (%) | 10.5 ± 5.0 | 5.4 ± 2.9 | 0.0290 |
| LAScd (%) | 6.5 (4.25–8) | 5.1 ± 2.5 | 0.1627 |
| LASct (%) | 1.5 (0.25–5.5) | 0 (0–1) | 0.0344 |
| RELAPS | 1.4 ± 0.5 | 13.5 (1.025–1.65) | 0.0874 |
| SR (n = 16) | AF (n = 7) | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.3 ± 5.1 | 0.8932 |
| LVESD (mm) | 31.3 ± 3.5 | 35.6 ± 6.8 | 0.1395 |
| IVS (mm) | 15.3 ± 2.5 | 15.3 ± 2.9 | 0.9731 |
| PW (mm) | 14.6 ± 3.0 | 15.3 ± 2.5 | 0.6361 |
| LVEF (%) | 54.9 ± 9.0 | 47.3 ± 14.8 | 0.0818 |
| LAD (mm) | 42.0 ± 3.7 | 46.9 ± 4.6 | 0.0292 |
| LA area (cm2) | 23.3 ± 3.8 | 27.6 ± 5.9 | 0.0606 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 57.6 ± 16.2 | 0.0381 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 71.6 ± 18.4 | 0.3152 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 5.2 ± 1.0 | 0.8409 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.8 ± 0.9 | 0.7380 |
| Average E/E′ | 18.0 ± 6.5 | 16.9 ± 5.0 | 0.8411 |
| DT (ms) | 200.5 (165.25–239) | 177.6 ± 35.3 | 0.3003 |
| Speckle-tracking measurement | |||
| GLS (%) | −10.6 ± 3.1 | −8.4 ± 2.3 | 0.1414 |
| GLS 4ch (%) | −10.0 ± 3.3 | −7.7 ± 1.8 | 0.0947 |
| GLS 2ch (%) | −11.4 ± 3.2 | −8.7 ± 2.8 | 0.0945 |
| GLS apex (%) | −10.6 ± 3.2 | −8.7 ± 2.3 | 0.2164 |
| LASr (%) | 10.5 ± 5.0 | 5.4 ± 2.9 | 0.0290 |
| LAScd (%) | 6.5 (4.25–8) | 5.1 ± 2.5 | 0.1627 |
| LASct (%) | 1.5 (0.25–5.5) | 0 (0–1) | 0.0344 |
| RELAPS | 1.4 ± 0.5 | 13.5 (1.025–1.65) | 0.0874 |
DT, deceleration time; GLS, global longitudinal strain; IVS, interventricular septal; LA area, left atrial area; LAD, left atrial dimension; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LAVI, left atrial volume index; LVDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSD, left ventricular end-systolic diameter; PW, posterior wall; RELAPS, relative apical sparing.
Baseline echocardiographic parameters
| SR (n = 16) | AF (n = 7) | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.3 ± 5.1 | 0.8932 |
| LVESD (mm) | 31.3 ± 3.5 | 35.6 ± 6.8 | 0.1395 |
| IVS (mm) | 15.3 ± 2.5 | 15.3 ± 2.9 | 0.9731 |
| PW (mm) | 14.6 ± 3.0 | 15.3 ± 2.5 | 0.6361 |
| LVEF (%) | 54.9 ± 9.0 | 47.3 ± 14.8 | 0.0818 |
| LAD (mm) | 42.0 ± 3.7 | 46.9 ± 4.6 | 0.0292 |
| LA area (cm2) | 23.3 ± 3.8 | 27.6 ± 5.9 | 0.0606 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 57.6 ± 16.2 | 0.0381 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 71.6 ± 18.4 | 0.3152 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 5.2 ± 1.0 | 0.8409 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.8 ± 0.9 | 0.7380 |
| Average E/E′ | 18.0 ± 6.5 | 16.9 ± 5.0 | 0.8411 |
| DT (ms) | 200.5 (165.25–239) | 177.6 ± 35.3 | 0.3003 |
| Speckle-tracking measurement | |||
| GLS (%) | −10.6 ± 3.1 | −8.4 ± 2.3 | 0.1414 |
| GLS 4ch (%) | −10.0 ± 3.3 | −7.7 ± 1.8 | 0.0947 |
| GLS 2ch (%) | −11.4 ± 3.2 | −8.7 ± 2.8 | 0.0945 |
| GLS apex (%) | −10.6 ± 3.2 | −8.7 ± 2.3 | 0.2164 |
| LASr (%) | 10.5 ± 5.0 | 5.4 ± 2.9 | 0.0290 |
| LAScd (%) | 6.5 (4.25–8) | 5.1 ± 2.5 | 0.1627 |
| LASct (%) | 1.5 (0.25–5.5) | 0 (0–1) | 0.0344 |
| RELAPS | 1.4 ± 0.5 | 13.5 (1.025–1.65) | 0.0874 |
| SR (n = 16) | AF (n = 7) | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.3 ± 5.1 | 0.8932 |
| LVESD (mm) | 31.3 ± 3.5 | 35.6 ± 6.8 | 0.1395 |
| IVS (mm) | 15.3 ± 2.5 | 15.3 ± 2.9 | 0.9731 |
| PW (mm) | 14.6 ± 3.0 | 15.3 ± 2.5 | 0.6361 |
| LVEF (%) | 54.9 ± 9.0 | 47.3 ± 14.8 | 0.0818 |
| LAD (mm) | 42.0 ± 3.7 | 46.9 ± 4.6 | 0.0292 |
| LA area (cm2) | 23.3 ± 3.8 | 27.6 ± 5.9 | 0.0606 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 57.6 ± 16.2 | 0.0381 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 71.6 ± 18.4 | 0.3152 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 5.2 ± 1.0 | 0.8409 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.8 ± 0.9 | 0.7380 |
| Average E/E′ | 18.0 ± 6.5 | 16.9 ± 5.0 | 0.8411 |
| DT (ms) | 200.5 (165.25–239) | 177.6 ± 35.3 | 0.3003 |
| Speckle-tracking measurement | |||
| GLS (%) | −10.6 ± 3.1 | −8.4 ± 2.3 | 0.1414 |
| GLS 4ch (%) | −10.0 ± 3.3 | −7.7 ± 1.8 | 0.0947 |
| GLS 2ch (%) | −11.4 ± 3.2 | −8.7 ± 2.8 | 0.0945 |
| GLS apex (%) | −10.6 ± 3.2 | −8.7 ± 2.3 | 0.2164 |
| LASr (%) | 10.5 ± 5.0 | 5.4 ± 2.9 | 0.0290 |
| LAScd (%) | 6.5 (4.25–8) | 5.1 ± 2.5 | 0.1627 |
| LASct (%) | 1.5 (0.25–5.5) | 0 (0–1) | 0.0344 |
| RELAPS | 1.4 ± 0.5 | 13.5 (1.025–1.65) | 0.0874 |
DT, deceleration time; GLS, global longitudinal strain; IVS, interventricular septal; LA area, left atrial area; LAD, left atrial dimension; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LAVI, left atrial volume index; LVDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSD, left ventricular end-systolic diameter; PW, posterior wall; RELAPS, relative apical sparing.
Echocardiographic examination of speckle tracking showed that LASr was significantly improved in ATTRwt-CA patients with SR by 1-year tafamidis treatment (10.5 ± 5.0% to 11.9 ± 5.3%, P = 0.0307) although GLS was not (−10.6 ± 3.1% to −11.3 ± 3.0%, P = 0.0608) (Figure 2). Regarding LA function, LAScd and LASct did not improve with tafamidis treatment in ATTRwt-CA patients with SR (Table 3). No significant changes were observed in the other echocardiographic parameters, except for an increase in the thickness of interventricular septum and RELAPSE by 1-year tafamidis treatment (Table 3).
Echocardiographic parameters before and 1-year tafamidis treatment in patients with SR
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.6 ± 6.4 | 0.0879 |
| LVESD (mm) | 31.3 ± 3.5 | 32.1 ± 5.3 | 0.3366 |
| IVS (mm) | 15.3 ± 2.5 | 15.7 ± 2.6 | 0.0285 |
| PW (mm) | 14.6 ± 3.0 | 14.8 ± 2.9 | 0.0550 |
| LVEF (%) | 54.9 ± 9.0 | 56.3 ± 7.1 | 0.2061 |
| LAD (mm) | 42.0 ± 3.7 | 42.5 ± 4.2 | 0.1038 |
| LA area (cm2) | 23.3 ± 3.8 | 24.5 ± 4.3 | 0.0594 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 46.8 ± 12.8 | 0.1281 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 78.0 ± 19.5 | 0.9852 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 4.8 ± 1.6 | 0.2150 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.5 (2.9–4.5) | 0.9527 |
| Average E/E′ | 18.0 ± 6.5 | 20.2 ± 7.4 | 0.3140 |
| DT (ms) | 200.5 (165.25–239) | 210.5 (167.75–227.75) | 0.8801 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −10.0 ± 3.3 | −11.4 ± 3.4 | 0.0751 |
| GLS 2ch (%) | −11.4 ± 3.2 | −11.2 ± 3.1 | 0.7271 |
| GLS apex (%) | −10.6 ± 3.2 | −11.3 ± 3.3 | 0.0583 |
| LAScd (%) | 6.5 (4.25–8) | 9 (6.25–11) | 0.0820 |
| LASct (%) | 1.5 (0.25–5.5) | 2 (0–5.75) | 0.9237 |
| RELAPS | 1.4 ± 0.5 | 1.7 ± 0.6 | 0.0023 |
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.6 ± 6.4 | 0.0879 |
| LVESD (mm) | 31.3 ± 3.5 | 32.1 ± 5.3 | 0.3366 |
| IVS (mm) | 15.3 ± 2.5 | 15.7 ± 2.6 | 0.0285 |
| PW (mm) | 14.6 ± 3.0 | 14.8 ± 2.9 | 0.0550 |
| LVEF (%) | 54.9 ± 9.0 | 56.3 ± 7.1 | 0.2061 |
| LAD (mm) | 42.0 ± 3.7 | 42.5 ± 4.2 | 0.1038 |
| LA area (cm2) | 23.3 ± 3.8 | 24.5 ± 4.3 | 0.0594 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 46.8 ± 12.8 | 0.1281 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 78.0 ± 19.5 | 0.9852 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 4.8 ± 1.6 | 0.2150 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.5 (2.9–4.5) | 0.9527 |
| Average E/E′ | 18.0 ± 6.5 | 20.2 ± 7.4 | 0.3140 |
| DT (ms) | 200.5 (165.25–239) | 210.5 (167.75–227.75) | 0.8801 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −10.0 ± 3.3 | −11.4 ± 3.4 | 0.0751 |
| GLS 2ch (%) | −11.4 ± 3.2 | −11.2 ± 3.1 | 0.7271 |
| GLS apex (%) | −10.6 ± 3.2 | −11.3 ± 3.3 | 0.0583 |
| LAScd (%) | 6.5 (4.25–8) | 9 (6.25–11) | 0.0820 |
| LASct (%) | 1.5 (0.25–5.5) | 2 (0–5.75) | 0.9237 |
| RELAPS | 1.4 ± 0.5 | 1.7 ± 0.6 | 0.0023 |
DT, deceleration time; GLS, global longitudinal strain; IVS, interventricular septal; LA area, left atrial area; LAD, left atrial dimension; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LAVI, left atrial volume index; LVDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSD, left ventricular end-systolic diameter; PW, posterior wall; RELAPS, relative apical sparing.
Echocardiographic parameters before and 1-year tafamidis treatment in patients with SR
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.6 ± 6.4 | 0.0879 |
| LVESD (mm) | 31.3 ± 3.5 | 32.1 ± 5.3 | 0.3366 |
| IVS (mm) | 15.3 ± 2.5 | 15.7 ± 2.6 | 0.0285 |
| PW (mm) | 14.6 ± 3.0 | 14.8 ± 2.9 | 0.0550 |
| LVEF (%) | 54.9 ± 9.0 | 56.3 ± 7.1 | 0.2061 |
| LAD (mm) | 42.0 ± 3.7 | 42.5 ± 4.2 | 0.1038 |
| LA area (cm2) | 23.3 ± 3.8 | 24.5 ± 4.3 | 0.0594 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 46.8 ± 12.8 | 0.1281 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 78.0 ± 19.5 | 0.9852 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 4.8 ± 1.6 | 0.2150 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.5 (2.9–4.5) | 0.9527 |
| Average E/E′ | 18.0 ± 6.5 | 20.2 ± 7.4 | 0.3140 |
| DT (ms) | 200.5 (165.25–239) | 210.5 (167.75–227.75) | 0.8801 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −10.0 ± 3.3 | −11.4 ± 3.4 | 0.0751 |
| GLS 2ch (%) | −11.4 ± 3.2 | −11.2 ± 3.1 | 0.7271 |
| GLS apex (%) | −10.6 ± 3.2 | −11.3 ± 3.3 | 0.0583 |
| LAScd (%) | 6.5 (4.25–8) | 9 (6.25–11) | 0.0820 |
| LASct (%) | 1.5 (0.25–5.5) | 2 (0–5.75) | 0.9237 |
| RELAPS | 1.4 ± 0.5 | 1.7 ± 0.6 | 0.0023 |
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 43.6 ± 5.5 | 44.6 ± 6.4 | 0.0879 |
| LVESD (mm) | 31.3 ± 3.5 | 32.1 ± 5.3 | 0.3366 |
| IVS (mm) | 15.3 ± 2.5 | 15.7 ± 2.6 | 0.0285 |
| PW (mm) | 14.6 ± 3.0 | 14.8 ± 2.9 | 0.0550 |
| LVEF (%) | 54.9 ± 9.0 | 56.3 ± 7.1 | 0.2061 |
| LAD (mm) | 42.0 ± 3.7 | 42.5 ± 4.2 | 0.1038 |
| LA area (cm2) | 23.3 ± 3.8 | 24.5 ± 4.3 | 0.0594 |
| LAVI (mL/m2) | 45.4 ± 13.8 | 46.8 ± 12.8 | 0.1281 |
| Doppler measurement | |||
| E velocity (m/s) | 77.9 ± 23.4 | 78.0 ± 19.5 | 0.9852 |
| E′ lateral (m/s) | 5.1 ± 1.4 | 4.8 ± 1.6 | 0.2150 |
| E′ septal (m/s) | 3.4 (3.125–4.15) | 3.5 (2.9–4.5) | 0.9527 |
| Average E/E′ | 18.0 ± 6.5 | 20.2 ± 7.4 | 0.3140 |
| DT (ms) | 200.5 (165.25–239) | 210.5 (167.75–227.75) | 0.8801 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −10.0 ± 3.3 | −11.4 ± 3.4 | 0.0751 |
| GLS 2ch (%) | −11.4 ± 3.2 | −11.2 ± 3.1 | 0.7271 |
| GLS apex (%) | −10.6 ± 3.2 | −11.3 ± 3.3 | 0.0583 |
| LAScd (%) | 6.5 (4.25–8) | 9 (6.25–11) | 0.0820 |
| LASct (%) | 1.5 (0.25–5.5) | 2 (0–5.75) | 0.9237 |
| RELAPS | 1.4 ± 0.5 | 1.7 ± 0.6 | 0.0023 |
DT, deceleration time; GLS, global longitudinal strain; IVS, interventricular septal; LA area, left atrial area; LAD, left atrial dimension; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LAVI, left atrial volume index; LVDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSD, left ventricular end-systolic diameter; PW, posterior wall; RELAPS, relative apical sparing.
However, LASr was not significantly changed (5.4 ± 2.9% to 4.9 ± 1.7%, P = 0.4571) although GLS deteriorated (−8.4 ± 2.3% to −6.8 ± 1.4%, P = 0.0267) in ATTRwt-CA patients with AF (Figure 3). Further, echocardiographic examination showed a significant decrease in LVEF and DT in the ATTRwt-CA patients with AF (Table 4).
LASr and GLS before and 1 year after tafamidis treatment. (A) LASr before and 1 year after tafamidis treatment in patients with wild-type transthyretin CA with SR. (B) GLS before and 1 year after tafamidis treatment in patients with wild-type transthyretin CA with SR. (C) LASr before and 1 year after tafamidis treatment in wild-type transthyretin CA with sinus AF. (D) GLS before and 1 year after tafamidis treatment in wild-type transthyretin CA with AF. Echocardiographic examination of speckle tracking showed that LAS was significantly improved in ATTRwt-CA patients with SR by 1-year tafamidis treatment (10.5 ± 5.0% to 11.9 ± 5.3%, P = 0.0307) although GLS was not (−10.6 ± 3.1% to −11.3 ± 3.0%, P = 0.0608). GLS, global longitudinal strain; LASr, left atrial reservoir strain.
Echocardiographic parameters before and 1-year tafamidis treatment in patients with AF
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 44.3 ± 5.1 | 43.9 ± 5.3 | 0.5098 |
| LVESD (mm) | 35.6 ± 6.8 | 36.0 ± 7.4 | 0.6748 |
| IVS (mm) | 15.3 ± 2.9 | 15.4 ± 2.6 | 0.3559 |
| PW (mm) | 15.3 ± 2.5 | 15.6 ± 2.5 | 0.1723 |
| LVEF (%) | 47.3 ± 14.8 | 39.3 ± 13.9 | 0.0139 |
| LAD (mm) | 46.9 ± 4.6 | 47.9 ± 3.4 | 0.2956 |
| LA area (cm2) | 27.6 ± 5.9 | 28.5 ± 4.4 | 0.4650 |
| LAVI (mL/m2) | 57.6 ± 16.2 | 60.0 ± 13.9 | 0.5843 |
| Doppler measurement | |||
| E velocity (m/s) | 71.6 ± 18.4 | 67.6 ± 13.4 | 0.2860 |
| E′ lateral (m/s) | 5.2 ± 1.0 | 6.4 ± 3.8 | 0.3922 |
| E′ septal (m/s) | 3.8 ± 0.9 | 3.5 ± 1.0 | 0.4924 |
| Average E/E′ | 16.9 ± 5.0 | 17.9 ± 8.2 | 0.5487 |
| DT (ms) | 177.6 ± 35.3 | 146.4 ± 40.1 | 0.0402 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −7.7 ± 1.8 | −6.9 ± 1.6 | 0.2919 |
| GLS 2ch (%) | −8.7 ± 2.8 | −6.5 ± 1.9 | 0.0014 |
| GLS apex (%) | −8.7 ± 2.3 | −6.7 ± 1.3 | 0.0364 |
| LAScd (%) | 5.1 ± 2.5 | 4.6 ± 2.2 | 0.2308 |
| LASct (%) | 0 (0–1) | 0 (0−2) | 0.5502 |
| RELAPS | 1.7 (1.6–1.8) | 2.2 (1.5–2.3) | 0.3051 |
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 44.3 ± 5.1 | 43.9 ± 5.3 | 0.5098 |
| LVESD (mm) | 35.6 ± 6.8 | 36.0 ± 7.4 | 0.6748 |
| IVS (mm) | 15.3 ± 2.9 | 15.4 ± 2.6 | 0.3559 |
| PW (mm) | 15.3 ± 2.5 | 15.6 ± 2.5 | 0.1723 |
| LVEF (%) | 47.3 ± 14.8 | 39.3 ± 13.9 | 0.0139 |
| LAD (mm) | 46.9 ± 4.6 | 47.9 ± 3.4 | 0.2956 |
| LA area (cm2) | 27.6 ± 5.9 | 28.5 ± 4.4 | 0.4650 |
| LAVI (mL/m2) | 57.6 ± 16.2 | 60.0 ± 13.9 | 0.5843 |
| Doppler measurement | |||
| E velocity (m/s) | 71.6 ± 18.4 | 67.6 ± 13.4 | 0.2860 |
| E′ lateral (m/s) | 5.2 ± 1.0 | 6.4 ± 3.8 | 0.3922 |
| E′ septal (m/s) | 3.8 ± 0.9 | 3.5 ± 1.0 | 0.4924 |
| Average E/E′ | 16.9 ± 5.0 | 17.9 ± 8.2 | 0.5487 |
| DT (ms) | 177.6 ± 35.3 | 146.4 ± 40.1 | 0.0402 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −7.7 ± 1.8 | −6.9 ± 1.6 | 0.2919 |
| GLS 2ch (%) | −8.7 ± 2.8 | −6.5 ± 1.9 | 0.0014 |
| GLS apex (%) | −8.7 ± 2.3 | −6.7 ± 1.3 | 0.0364 |
| LAScd (%) | 5.1 ± 2.5 | 4.6 ± 2.2 | 0.2308 |
| LASct (%) | 0 (0–1) | 0 (0−2) | 0.5502 |
| RELAPS | 1.7 (1.6–1.8) | 2.2 (1.5–2.3) | 0.3051 |
DT, deceleration time; GLS, global longitudinal strain; IVS, interventricular septal; LA area, left atrial area; LAD, left atrial dimension; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LAVI, left atrial volume index; LVDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSD, left ventricular end-systolic diameter; PW, posterior wall; RELAPS, relative apical sparing.
Echocardiographic parameters before and 1-year tafamidis treatment in patients with AF
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 44.3 ± 5.1 | 43.9 ± 5.3 | 0.5098 |
| LVESD (mm) | 35.6 ± 6.8 | 36.0 ± 7.4 | 0.6748 |
| IVS (mm) | 15.3 ± 2.9 | 15.4 ± 2.6 | 0.3559 |
| PW (mm) | 15.3 ± 2.5 | 15.6 ± 2.5 | 0.1723 |
| LVEF (%) | 47.3 ± 14.8 | 39.3 ± 13.9 | 0.0139 |
| LAD (mm) | 46.9 ± 4.6 | 47.9 ± 3.4 | 0.2956 |
| LA area (cm2) | 27.6 ± 5.9 | 28.5 ± 4.4 | 0.4650 |
| LAVI (mL/m2) | 57.6 ± 16.2 | 60.0 ± 13.9 | 0.5843 |
| Doppler measurement | |||
| E velocity (m/s) | 71.6 ± 18.4 | 67.6 ± 13.4 | 0.2860 |
| E′ lateral (m/s) | 5.2 ± 1.0 | 6.4 ± 3.8 | 0.3922 |
| E′ septal (m/s) | 3.8 ± 0.9 | 3.5 ± 1.0 | 0.4924 |
| Average E/E′ | 16.9 ± 5.0 | 17.9 ± 8.2 | 0.5487 |
| DT (ms) | 177.6 ± 35.3 | 146.4 ± 40.1 | 0.0402 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −7.7 ± 1.8 | −6.9 ± 1.6 | 0.2919 |
| GLS 2ch (%) | −8.7 ± 2.8 | −6.5 ± 1.9 | 0.0014 |
| GLS apex (%) | −8.7 ± 2.3 | −6.7 ± 1.3 | 0.0364 |
| LAScd (%) | 5.1 ± 2.5 | 4.6 ± 2.2 | 0.2308 |
| LASct (%) | 0 (0–1) | 0 (0−2) | 0.5502 |
| RELAPS | 1.7 (1.6–1.8) | 2.2 (1.5–2.3) | 0.3051 |
| Baseline | 1-year | P-value | |
|---|---|---|---|
| 2D measurement | |||
| LVEDD (mm) | 44.3 ± 5.1 | 43.9 ± 5.3 | 0.5098 |
| LVESD (mm) | 35.6 ± 6.8 | 36.0 ± 7.4 | 0.6748 |
| IVS (mm) | 15.3 ± 2.9 | 15.4 ± 2.6 | 0.3559 |
| PW (mm) | 15.3 ± 2.5 | 15.6 ± 2.5 | 0.1723 |
| LVEF (%) | 47.3 ± 14.8 | 39.3 ± 13.9 | 0.0139 |
| LAD (mm) | 46.9 ± 4.6 | 47.9 ± 3.4 | 0.2956 |
| LA area (cm2) | 27.6 ± 5.9 | 28.5 ± 4.4 | 0.4650 |
| LAVI (mL/m2) | 57.6 ± 16.2 | 60.0 ± 13.9 | 0.5843 |
| Doppler measurement | |||
| E velocity (m/s) | 71.6 ± 18.4 | 67.6 ± 13.4 | 0.2860 |
| E′ lateral (m/s) | 5.2 ± 1.0 | 6.4 ± 3.8 | 0.3922 |
| E′ septal (m/s) | 3.8 ± 0.9 | 3.5 ± 1.0 | 0.4924 |
| Average E/E′ | 16.9 ± 5.0 | 17.9 ± 8.2 | 0.5487 |
| DT (ms) | 177.6 ± 35.3 | 146.4 ± 40.1 | 0.0402 |
| Speckle-tracking measurement | |||
| GLS 4ch (%) | −7.7 ± 1.8 | −6.9 ± 1.6 | 0.2919 |
| GLS 2ch (%) | −8.7 ± 2.8 | −6.5 ± 1.9 | 0.0014 |
| GLS apex (%) | −8.7 ± 2.3 | −6.7 ± 1.3 | 0.0364 |
| LAScd (%) | 5.1 ± 2.5 | 4.6 ± 2.2 | 0.2308 |
| LASct (%) | 0 (0–1) | 0 (0−2) | 0.5502 |
| RELAPS | 1.7 (1.6–1.8) | 2.2 (1.5–2.3) | 0.3051 |
DT, deceleration time; GLS, global longitudinal strain; IVS, interventricular septal; LA area, left atrial area; LAD, left atrial dimension; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LAVI, left atrial volume index; LVDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSD, left ventricular end-systolic diameter; PW, posterior wall; RELAPS, relative apical sparing.
A significant correlation was noted between changes in LASr and GLS in over 1-year tafamidis treatment (R2 = 0.599, P = 0.0004) (Figure 4). However, no significant correlation was determined between the change in LASr and the change in average E/E′ in over 1-year tafamidis treatment (Figure 4).
Correlation between change in LASr and GLS or average of E/E′ over 1-year tafmidis treatment. (A) Correlation between changes in the LASr and GLS over 1 year of tafamidis treatment. (B) Correlation between changes in LASr and average E/E′ over 1 year of tafadis treatment. GLS, global longitudinal strain; LASr, left atrial reservoir strain.
The inter-observer variability between the two blinded readers with ICC was good to excellent: GLS, 0.99 [confidence interval (CI), 0.98–0.99]; LASr, 0.98 (CI, 0.91–0.99); LAScd, 0.90 (CI, 0.64–0.97); and LASct, 0.93 (CI, 0.74–0.98).
Discussion
This study demonstrated that 1-year tafamidis treatment improved LASr and LA function, but not GLS or LV function, in ATTRwt-CA patients with SR, but not in those with AF.
Previous studies have demonstrated that tafamidis prevented the worsening of LV function using GLS 8.5 (median) to 18 months after the administration of tafamidis; however, it did not improve GLS.8–11 These results are consistent with our data.
LA function using 2D-STE has been studied in CA, and it showed severely impaired LA function in CA.2 It has been reported that LAS may be useful for discriminating CA from other diseases with LV hypertrophy15–17 and predicting prognosis in patients with CA.18,19
Recently, only one report has demonstrated that LAS was not changed by tafamidis treatment, although treatment-naïve ATTR-CM patients showed progression of LAS.11 However, the study was performed on ATTR-CM patients, including AF patients. As the mechanism for the development of AF in ATTR-CA is multifaceted,20 tafamidis treatment alone may not be sufficient to improve LA function. We demonstrated that LASr was significantly lower in patients with AF than in those with SR in the present study. Thus, one of the other possibilities is that it may take longer for LASr to improve with tafamidis treatment in patients with AF than with SR.
Moreover, we excluded patients who underwent cardiac device implantation, mitral valve replacement, or catheter ablation for AF, even though they had SR, because these may affect LA function. Thus, the exclusion of these patients, in addition to AF patients, may have been the reason for the good results obtained because the effect of pure tafamidis in LA function is related to amyloidosis in ATTRwt-CA patients with SR.
However, the precise mechanism of LAS improvement by tafamidis treatment is unknown.
ATTR-CA includes significant infiltration of the atrial walls with progressive loss of atrial function and increased stiffness, which are strong independent predictors of mortality.14
The involvement of the atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, amyloid infiltration into the atrial wall, and cardiotoxic damage to atrial cardiomyocytes by amyloid precursors (especially light chains).21
In patients with heart failure with preserved ejection fraction, LASr values decreased with worsening LV diastolic dysfunction categorized by mitral E/A ratio, E-wave deceleration time, average E/E′ and peak pulmonary systolic pressure using echocardiography,22 or LASr correlated with GLS and E/E′.23
Nochioka et al.2 have demonstrated that LV GLS was correlated with LASr in CA.
However, LASr and LA contraction strain correlated with E/E′ (a marker of diastolic dysfunction) and LAVI only in AL-CA but not in ATTR-CA.24
Further, we revealed that the change in LASr was correlated with the change in GLS but not with the average E/E′ in patients with ATTRwt-CA.
The reduced LASr may represent LV dysfunction combined with intrinsic LA dysfunction from amyloid infiltration.15,23,25
Recent studies using scintigraphy to detect amyloid deposition have shown that tafamidis decreases the cardiac uptake of 99mTc-hydroxyl-methylenediphosphonate or 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid in ATTR-CA.26–28
Therefore, in this study, the decrease in amyloid deposition in the LA and LV may be related to the improvement in LASr.
However, it was not determined why GLS did not improve by 1-year tafamidis treatment. This may be due to greater amyloid accumulation in the LV than in the LA.
Among the strain data from all four chambers, the LAS had the strongest association with survival in CA.18 The LAS may be more sensitive in detecting abnormalities in the CA, which may be another possible reason. However, further studies are required to elucidate these underlying mechanisms.
Limitation
The present study had several limitations. This was a single-centre retrospective study with a small sample size that may not be sufficient to detect statistical significance, especially in ATTRwt-CA patients with AF. However, patients were strictly selected to ensure that the effects of tafamidis on cardiac function were mainly related to amyloidosis, and the LA function in our study was similar to that in larger studies. Moreover, effects of tafamidis on GLS and ALS were evaluated only 1-year tafamidis treatment although the main outcomes of ATTR-ACT only started emerging at 18 months.4 Thus, larger and long-term studies are needed to validate these results.
Conclusion
Tafamidis treatment may be more effective for LA function than for LV function in patients with ATTRwt-CA with SR. However, tafamidis treatment did not improve the cardiac function in patients with ATTRwt-CA and AF.
Funding
None declared.
Data availability
Data are available on request.
References
Author notes
Conflict of interest: None declared.
