Key result
Non-sustained VT in ATTR-CM is linked to increased sudden cardiac death, without altering overall mortality.
Why the study?
With advances in diagnostic modalities and disease-specific therapies prolonging survival in ATTR-CM, the frequency and prognostic relevance of ventricular arrhythmias require re-evaluation, as ICD recommendations for primary prevention of SCD have historically been conservative.
Does the presence of ventricular arrhythmias (nsVT and sVT) on Holter monitoring predict all-cause mortality and sudden cardiac death in patients with ATTR-cardiomyopathy?
Cohort (n=266)
Yes
Does the presence of ventricular arrhythmias (nsVT and sVT) on Holter monitoring predict all-cause mortality and sudden cardiac death in patients with ATTR-cardiomyopathy?
In patients with ATTR-CM, non-sustained VT on Holter monitoring is common (30%) and reflects advanced disease severity with a higher risk of sudden cardiac death, though it is not an independent predictor of all-cause mortality.
nsVT on Holter signals higher SCD risk in ATTR-CM but not independent all-cause mortality; leaves open its value for arrhythmia-guided risk stratification.
Background ATTR-cardiomyopathy (ATTR-CM) is an infiltrative disease that causes heart failure, conduction disturbances and arrhythmias. Historically considered untreatable, guideline recommendations for primary prevention of sudden cardiac death (SCD) with ICD have been conservative. With advances in diagnostic modalities and disease-specific therapies prolonging survival, the prognostic relevance of ventricular arrhythmias (VAs) merits re-evaluation. We aimed to determine the frequency of VA in ATTR-CM and evaluate their association with all-cause mortality. Methods We prospectively enrolled patients with confirmed ATTR-CM from two tertiary amyloidosis centers between 2017 and 2025. All participants underwent Holter ECG monitoring alongside detailed clinical assessments. VAs during Holter were categorized as sustained ventricular tachycardia (sVT) and non-sustained ventricular tachycardia (nsVT). Patients survival status was ascertained through structured telephone follow-up and review of the civil death registry. Survival differences were evaluated using Kaplan-Meier analysis and log-rank tests. Predictors of mortality were analyzed using multivariable logistic regression models. Results In this unselected cohort of 266 patients, occurrence of nsVTs was frequent (79/261, 30%), whereas sVTs were rarely detected (2/257, 0.8%). Over an observation period of 60±42 months, 40 of 266 patients died. The main causes of death were heart failure (n=12), SCD (n=5), and non-cardiac death (n=5, incl. stroke, infection, malignancy), while cause of death remained unclear in 18 patients. Presence of nsVT on Holter was significantly associated with an increased risk of SCD (5% vs. 0.6%, p=0.031), but not all-cause mortality (29% vs. 13%, p=0.19, figure 1). By contrast, one of the two patients with sVTs died during follow-up (all-cause mortality 50% vs. 17%, p=0.003). Overall, nsVTs were associated with advanced disease stage, such as higher cardiac biomarkers and worse echocardiographic parameters, including greater interventricular septal diameter (IVSd), lower ejection fraction (LVEF) and reduced tricuspid annular plane systolic excursion (TAPSE, Table 1). In a multivariable logistic regression model age (OR 1.09, p=0.023) and NT-proBNP (OR 1.00, p=0.001) were independent predictors while nsVTs (OR 2.24, p=0.061) and mean heart rate (OR 0.97, p=0.070) were retained only as potential predictors for all-cause mortality. Conclusion In this cohort of ATTR-CM patients, nsVTs were common in Holter monitoring and were associated with parameters of disease severity. The presence of nsVTs translated into higher risk of SCD, but not all-cause mortality. By contrast, sustained VTs occurred rarely but showed an adverse prognosis. Larger studies with long-term follow-up in ATTR-CM patients are warranted to clarify which individuals might be at risk of SCD and potentially even benefit from prophylactic ICD therapy.Figure 1Table 1
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Knoll et al. (2026) conducted a cohort in ATTR-cardiomyopathy (ATTR-CM) (n=266). Non-sustained ventricular tachycardia (nsVT) on Holter ECG vs. No non-sustained ventricular tachycardia was evaluated on All-cause mortality (OR 2.24, p=0.19). Non-sustained VT on Holter in ATTR-CM increased the risk of sudden cardiac death (5% vs 0.6%, p=0.031) but not all-cause mortality (29% vs 13%, p=0.19).
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