Prognostic Value of [99mTc]Tc-DPD Quantitative SPECT/CT in Patients with Suspected and Confirmed Amyloid Transthyretin–Related Cardiomyopathy and Preserved Left Ventricular Function

Federico Caobelli; Nasir Gözlügöl; Adam Bakula; Axel Rominger; Robin Schepers; Stefan Stortecky; Lukas Hunziker Munsch; Stephan Dobner; Christoph Gräni

doi:10.2967/jnumed.123.266926

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FIGURE 1.
Study flowchart.
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FIGURE 2.
Kaplan–Meyer curves highlighting predictive role of myocardial SUV_max ≥ 7 in whole cohort (n = 144). (A) In patients with preserved LVEF, SUV_max ≥ 7 as separator predicted higher rate of MACEs. (B) Conversely, no predictive role was seen in patients with already-impaired LVEF.
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FIGURE 3.
Kaplan–Meyer curves highlighting predictive role of myocardial SUV_max ≥ 7 in patients with confirmed ATTR-CM (n = 99). Similarly to what was observed for whole cohort, SUV_max ≥ 7 predicted higher rate of MACEs in patients with preserved LVEF (A) but not in patients with already-impaired LVEF (B).

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TABLE 1.

Clinical Characteristics of Whole Patient Sample

Characteristic	All patients with suspected ATTR-CM (n = 144)	Patients with preserved LVEF (≥50%, n = 98)	Patients with impaired LVEF (<50%, n = 46)	P
Clinical parameters
BMI (kg/m²)	26.4 ± 4.8	26.7 ± 4.4	25.1 ± 5.4	0.01^*
NYHA functional class ≥ III	38 (26.4%)	24 (24.5%)	14 (30.4%)	0.29
Age (y)	81.5 ± 5.8	80.2 ± 8.2	79.7 ± 7.5	0.39
Male sex	127 (88.2%)	87 (88.8%)	40 (86.7%)	0.34
Laboratory parameters
T-troponin (ng/L)	42 (37)	51.8 ± 39.5	60.0 ± 44.9	0.18
Median nT-proBNP (pg/mL)	2,294 (IQR, 3,368)	1,540.0 (IQR, 3,193.0)	2,925.0 (IQR, 2,452.0)	0.01^*
Median creatinine-phosphokinase (IU/L)	88 (IQR, 73)	88.0 (IQR, 80.0)	104.4 (IQR, 67.0)	0.68
Echocardiographic parameters
LVEDD (mm)	45.8 ± 7.0	44.7 ± 6.9	48.7 ± 6.3	0.01^*
LVEF (%)	53.3 ± 10.8	58.8 ± 5.9	39.3 ± 7.2	<0.001^*
Maximum wall thickness (mm)	15.9 ± 4.6	15.6 ± 3.1	16.5 ± 7.1	0.51
Left ventricular mass index (g/m²)	138.13 ± 52.6	131.1 ± 41.0	156.9 ± 71.8	0.09
Scintigraphy
Perugini score 0	43 (29.9%)	29 (29.6%)	14 (30.4%)	0.43
Perugini score 1	9 (6.3%)	6 (6.1%)	3 (6.5%)	0.60
Perugini score 2	65 (45.1%)	48 (49.0%)	17 (37.0%)	0.18
Perugini score 3	27 (18.8%)	16 (16.3%)	11 (23.9%)	0.19
SUV_max	9.3 ± 6.7	9.9 ± 7.0	7.9 ± 5.9	0.18
SUV_peak	8.7 ± 6.3	9.2 ± 6.6	7.3 ± 5.5	0.17
Therapy
Ace inhibitors	36 (25.0%)	28 (28.6%)	8 (17.4%)	0.28
Angiotensin-II inhibitors	49 (34.0%)	36 (36.7%)	13 (28.3%)	0.51
Sacubitril/valsartan	3 (2.1%)	1 (1.0%)	2 (4.3%)	0.18
β-blockers	63 (43.8%)	36 (36.7%)	27 (58.7%)	<0.001^*
Spironolactone	21 (14.6%)	11 (11.2%)	10 (2.2%)	0.03^*
SGLT-2 inhibitors	19 (13.2%)	8 (8.2%)	11 (23.9%)	0.003^*
Diuretics	86 (39.7%)	60 (61.2%)	26 (56.5%)	0.22
Calcium channels antagonists	32 (22.2%)	28 (28.6%)	4 (8.6%)	0.02^*
Amiodaron	8 (5.6%)	5 (5.1%)	3 (6.5%)	0.38
Tafamidis	53 (36.8%)	38 (38.8%)	15 (32.6%)	0.30

↵* Statistically significant.
NYHA = New York Heart Association.
Qualitative data are number and percentage; continuous data are mean ± SD unless otherwise indicated. Therapies other than transthyretin stabilizer were recorded at baseline; therapy with tafamidis (if any) was started after final diagnosis was reached.

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TABLE 2.

Clinical Characteristics of Patients with Confirmed ATTR-CM

Characteristic	Patients with confirmed ATTR-CM (n = 99)	Patients with preserved LVEF (≥50%, n = 69)	Patients with impaired LVEF (<50%, n = 30)	P
Clinical parameters
BMI (kg/m²)	26.1 ± 4.6	26.3 ± 4.0	25.7 ± 5.8	0.04^*
NYHA functional class ≥ III	27 (27.3%)	17 (24.6%)	10 (33.3%)	0.26
Age (y)	81.5 ± 5.9	81.5 ± 5.8	81.4 ± 6.3	0.74
Male sex	91 (91.9%)	64 (92.8%)	27 (90.0%)	0.29
Laboratory parameters
T-troponin (ng/L)	57.8 ± 41.9	54.2 ± 39.7	67.0 ± 46.9	0.08
Median nT-proBNP (pg/mL)	2533.0 (IQR, 3301.0)	1564.0 (IQR, 3230.0)	2914.2 (IQR, 2364.0)	0.09
Median creatinine-phosphokinase (IU/L)	88.0 (IQR, 75.0)	88.0 (IQR, 89.0)	86.5 (IQR, 61.0)	0.43
Echocardiographic parameters
LVEDD (mm)	45.2 ± 7.1	43.8 ± 6.8	48.9 ± 6.7	0.02^*
LVEF (%)	53.4 ± 10.2	58.5 ± 6.0	40.1 ± 5.6	<0.001^*
Maximum wall thickness (mm)	16.1 ± 3.1	16.2 ± 3.1	16.0 ± 3.0	0.73
Left ventricular mass index (g/m²)	139.1 ± 41.9	133.0 ± 42.3	154.9 ± 37.2	0.05
Scintigraphy
Perugini score 0	0 (0%)	0 (0%)	0 (0%)	—
Perugini score 1	7 (7.1%)	5 (7.2%)	2 (6.7%)	0.64
Perugini score 2	65 (65.7%)	48 (69.6%)	17 (56.7%)	0.16
Perugini score 3	27 (27.3%)	16 (23.2%)	11 (36.6%)	0.13
SUV_max	12.6 ± 5.7	13.3 ± 5.4	10.8 ± 4.8	0.04^*
SUV_peak	11.8 ± 5.0	12.5 ± 5.1	10.1 ± 4.5	0.03^*
Therapy
Ace inhibitors	26 (26.3%)	21 (30.4%)	5 (16.7%)	0.16
Angiotensin-II inhibitors	34 (34.3%)	23 (33.3%)	11 (36.7%)	0.37
Sacubitril/valsartan	2 (2.2%)	1 (1.4%)	1 (3.3%)	0.50
β-blockers	43 (43.4%)	24 (34.8%)	19 (63.3%)	0.003^*
Spironolactone	18 (18.2%)	11 (15.9%)	7 (23.3%)	0.22
SGLT-2 inhibitors	15 (15.2%)	7 (10.1%)	8 (26.7%)	0.03^*
Diuretics	67 (67.7%)	47 (68.1%)	20 (66.7%)	0.47
Calcium channels antagonists	23 (23.2%)	20 (29.0%)	3 (10.0%)	0.04^*
Amiodaron	5 (5.5%)	4 (5.8%)	1 (3.3%)	0.55
Tafamidis	53 (53.5%)	38 (55.1%)	15 (50.0%)	0.40

↵* Statistically significant.
NYHA = New York Heart Association.
Qualitative data are number and percentage; continuous data are mean ± SD unless otherwise indicated. Therapies other than transthyretin stabilizer were recorded at baseline; therapy with tafamidis (if any) was started after final diagnosis was reached.

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TABLE 3.

Hazard Ratio of Relevant Clinical and Imaging-Derived Parameters for Prediction of MACEs in Whole Patient Sample (n = 144)

	All patients with suspected ATTR-CM (n = 144)			Patients with preserved LVEF (≥50%, n = 98)			Patients with impaired LVEF (<50%, n = 46)
Parameter	HR	95% CI	P	HR	95% CI	P	HR	95% CI	P
BMI	0.980	0.927–1.037	0.489	0.982	0.917–1.051	0.594	0.962	0.855–1.083	0.521
NT-proBNP	1.0	1.0–1.0	0.127	1.0	1.0–1.0	0.168	1.0	1.0–1.0	0.168
LVEDD	0.987	0.709–2.357	0.590	0.983	0.931–1.038	0.540	0.998	0.903–1.103	0.967
Perugini score	1.183	0.896–1.561	0.236	1.306	0.934–1.825	0.118	0.916	0.541–1.552	0.745
SUV_max (continuous)	1.014	0.970–1.059	0.540	1.028	0.980–1.079	0.258	0.923	0.820–1.039	0.186
SUV_peak (continuous)	1.015	0.969–1.063	0.519	1.031	0.980–1.085	0.244	0.918	0.810–1.042	0.185
SUV_max ≥ 7	1.752	0.925–3.317	0.090	2.875	1.230–6.710	0.015^*	0.525	0.164–1.687	0.280

↵* Statistically significant.

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TABLE 4.

Hazard Ratio of Relevant Clinical and Imaging-Derived Parameters for Prediction of MACEs in Patients with Confirmed ATTR-CM (n = 99)

	All patients with suspected ATTR-CM (n = 99)			Patients with preserved LVEF (≥50%, n = 69)			Patients with impaired LVEF (<50%, n = 30)
Parameter	HR	95% CI	P	HR	95% CI	P	HR	95% CI	P
BMI	1.006	0.940–1.076	0.867	0.999	0.916–1.090	0.984	1.004	0.896–1.126	0.939
NT-proBNP	1.0	1.0–1.0	0.059	1.0	1.0–1.0	0.240	1.0	1.0–1.0	0.612
LVEDD	0.975	0.929–1.024	0.320	0.970	0.914–1.030	0.323	0.988	0.890– 1.097	0.830
Perugini score	1.115	0.645–1.929	0.696	1.358	0.684–2.697	0.358	0.825	0.336–2.028	0.675
SUV_max (continuous)	0.996	0.939–1.059	0.893	1.009	0.941–1.083	0.800	0.877	0.741–1.038	0.127
SUV_peak (continuous)	0.997	0.934–1.064	0.928	1.012	0.939–1.070	0.760	0.868	0.725–1.040	0.125
SUV_max ≥ 7	1.939	0.682–5.510	0.214	6.892^*	—	0.009^†	0.420	0.112–1.574	0.198

↵* Given lack of events in patients with SUV_max < 7 in this group, this value represents global Wald χ², calculated with log-Poisson regression analysis.
↵† Statistically significant.
HR = hazard ratio.