This study was a retrospective chart review conducted at a single academic medical center. We identified and included all consecutive patients diagnosed with ATTR-CM who underwent implantation of a PPM, ICD, or CRT device between April 2012 and September 2022. ATTR-CM diagnosis was confirmed through a combination of clinical evaluation, imaging (including technetium-99m pyrophosphate scintigraphy or cardiac magnetic resonance), and/or endomyocardial biopsy, in accordance with established guidelines. Patients were required to have a CIED implanted for standard indications, such as bradyarrhythmia, conduction disturbance, or HF management. Exclusion criteria included patients with incomplete medical records or those with alternative cardiomyopathies (such as light-chain amyloidosis). A total of 105 patients met the inclusion criteria. The study was approved by the institutional review board, and informed consent was waived due to the retrospective nature of the chart review.

Patients were categorized into three groups based on their device type and RVP burden at the time of device implantation: (1) PPM/ICD with low RVP (RVP burden <40%, N = 31), (2) PPM/ICD with high RVP (RVP burden ≥40%, N = 38), and (3) CRT-pacemaker and CRT-defibrillator ( N = 36). Among the CRT group, 33 (91.7%) patients received CRT upfront, while 3 (8.3%) were upgraded from prior single or dual-chamber devices. RVP burden was assessed via device interrogation data obtained at the first postimplant assessment, either prior to hospital discharge for inpatient procedures or the first follow-up visit for outpatient procedures. Baseline characteristics were extracted from electronic medical records, including demographics, comorbidities, laboratory values, and echocardiographic parameters. Disease severity was classified using the National Amyloidosis Center (NAC) staging system, which categorizes patients based on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and glomerular filtration rate (GFR) thresholds as follows: Stage I (NT-proBNP ≤3,000 ng/L and GFR ≥ 45 ml/min/1.73 m²), Stage III (NT-proBNP > 3,000 ng/L and GFR < 45 ml/min/1.73 m²), and remainder as Stage II. ^, Follow-up data were collected retrospectively through clinic visits and hospital records. The last measurement of device parameters is from the most recent available device interrogation. Outcomes of interest included all-cause mortality, HF rehospitalization, and changes in LVEF over time.

Continuous variables were summarized as mean ± standard deviation or median (interquartile range [IQR]), depending on distribution normality assessed via Shapiro–Wilk tests. Categorical variables were presented as frequencies and percentages. Baseline comparisons across groups were performed using Pearson’s chi-squared test or Fisher’s exact test for categorical variables, and one-way ANOVA or Kruskal–Wallis rank sum test for continuous variables, as appropriate. For survival analysis, Fine–Gray proportional subdistribution hazard models were employed to account for orthotopic heart transplant as a competing risk for all-cause mortality. Incidence rate ratios (IRRs) with 95% CIs were used to evaluate HF rehospitalization rates, modeled via negative binomial regression to handle overdispersion and recurrent events. Linear mixed-effects models were applied to assess longitudinal changes in LVEF, accounting for repeated measures and adjusting for time as a fixed effect. All multivariable models were adjusted for clinically relevant covariates: age, gender, race (White vs Black), NAC staging system, initial LVEF, and presence of atrial fibrillation (AF). Analyses were conducted using RStudio (Version 2024.12.1 + 563). p Values <0.05 were considered statistically significant.

The total 105 patients with ATTR-CM and CIEDs, with a mean age of 80 ± 8 years, 75.2% male, and 65.7% Caucasian, were included in this study. Among the 105 patients included, 60 (57.1%) were diagnosed by PYP scintigraphy with confirmatory imaging findings, and 45 (42.9%) underwent endomyocardial biopsy with pathologic confirmation of ATTR-CM. Device implantation indications included 26 patients (24.8%) for bradyarrhythmia (including sinus node dysfunction and symptomatic bradycardia), 41 patients (39.0%) for high-grade conduction disturbances, and 38 patients (36.2%) for HF management. Median initial LVEF was 40% (IQR: 30% to 55%), median NT-proBNP was 3,016 pg/ml (IQR: 1,230 to 6,610), and mean GFR was 51.5 ± 16.1 ml/min/1.73 m². There were 49 (46.7%) patients who were treated with tafamidis. Sixty-six (62.9%) patients had wild-type ATTR-CM, whereas 39 (37.1%) had hereditary ATTR-CM. AF was present in 44.8%, coronary artery disease in 14.3%, and neurologic disorders in 21.9%. Median follow-up time was 3.1 (IQR: 1.3 to 4.9) years. Baseline comparisons revealed significant differences in sex and initial LVEF. Follow-up time differed significantly, with the low RVP group having the longest median duration (3.9 years, IQR: 3.1 to 6.9). Regarding NAC staging, significant differences were observed for Stage I and Stage II, but not for Stage III. The high RVP (65%) and CRT (80%) groups had a higher prevalence of advanced NAC staging (Stages II/III) compared to the low RVP group (55%). The detailed baseline characteristics are summarized in Table 1 .

Over the follow-up period, there were 55 deaths and 4 orthotopic heart transplant events. The high RVP group had significantly worse survival compared to the low RVP group (hazard ratio 6.24, 95% CI: 2.82 to 13.83, p < 0.001). The CRT group showed significantly better survival than high RVP group (hazard ratio 3.03, 95% CI: 1.41 to 6.52, p = 0.005) and nonsignificant difference compared to low RVP group ( Figure 1 ). Independent predictors of mortality included NAC Stage II and Stage III relative to Stage I; presence of AF; and lower initial LVEF. Gender and race did not show significant prediction value ( Table 2 ).

Cumulative incidence of death by device group. This cumulative incidence plot illustrates the probability of death over time (years) for PPM/ICD with high RVP (blue), PPM/ICD with low RVP (green), and CRT (orange) groups. Survival analysis was performed using Fine–Gray models with OHT as a competing risk. Models were adjusted for NAC staging, initial LVEF, atrial fibrillation, race, and gender. CRT = cardiac resynchronization therapy; ICD = implantable cardioverter-defibrillator; NAC = National Amyloidosis Center; OHT = orthotopic heart transplantation; PPM = permanent pacemaker.

Table 2

Clinical outcomes: survival, heart failure rehospitalization, and LVEF change

Comparison/variable	Effect estimate	95% CI	p value
Survival analysis (hazard ratios)
High vs low RVP	6.24	2.82–13.83	<0.001
CRT vs low RVP	2.06	0.89–4.76	0.09
High RVP vs CRT	3.03	1.41–6.52	0.005
NAC Stage I	Reference
NAC Stage II	2.48	1.06–5.81	0.037
NAC Stage III	4.81	2.04–11.34	<0.001
Atrial fibrillation	2.01	1.08–3.75	0.028
Initial LVEF (per 1% decrease)	1.03	1.01–1.06	0.006
Gender (male vs female)	1.55	0.68–3.50	0.30
Race (White vs Black)	0.57	0.27–1.22	0.15
Heart failure rehospitalization (incidence rate ratios)
High vs low RVP	5.76	2.71–12.25	<0.001
CRT vs low RVP	3.35	1.66–6.74	<0.001
High RVP vs CRT	1.72	0.89–3.30	0.11
NAC Stage I	Reference
NAC Stage II	3.27	1.74–6.16	<0.001
NAC Stage III	4.29	2.01–9.18	<0.001
Initial LVEF ≤ 15%	107.65	6.61–1,751.27	0.003
Race (White vs Black)	0.49	0.28–0.92	0.022
Atrial fibrillation	0.96	0.56–1.65	0.87
Gender (male vs female)	1.50	0.82–2.74	0.20
LVEF change (mean difference, %)
High RVP vs CRT	+4.47	−1.90 to 10.90	0.17
Low RVP vs CRT	+0.48	−5.73 to 6.69	0.88
High vs low RVP	+3.99	−3.03 to 10.99	0.26
NAC Stage I	Reference
NAC Stage II	+0.22	−5.49 to 5.92	0.94
NAC Stage III	−9.74	−17.72 to −1.75	0.017
Initial LVEF (per 1% increase)	−0.49	−0.72 to −0.25	<0.001
Race (White vs Black)	+8.76	2.75 to 14.77	0.005
Atrial fibrillation	−0.95	−5.70 to 3.79	0.69
Gender (male vs female)	−2.00	−8.18 to 4.19	0.53

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