Dataset Information

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy.

ABSTRACT:

Background

Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular arrhythmias, particularly ventricular tachycardias (VTs), in wtATTR-CM is unclear. With the development of targeted therapies and improved overall prognosis, there is an unmet need to identify patients at high risk for VTs who might benefit from ICD therapy.

Methods

Between 2017 and 2022, 72 patients diagnosed with wtATTR-CM were prospectively evaluated for the presence of ventricular arrhythmias using a Holter ECG. VTs were defined as >3 consecutive beats with a heart rate > 100 beats per minute originating from a ventricle.

Results

The incidence of VTs was 44% (n = 32/72) in unselected wtATTR-CM patients. Patients with VT showed significantly more severe left ventricular (LV) hypertrophy (septum diameter 21 ± 2.6 vs. 19 ± 3.0 mm, p = 0.006), reduced LV ejection fraction (47 ± 8 vs. 52 ± 8%, p = 0.014) and larger left atria (32 ± 7 vs. 28 ± 6 mm², p = 0.020), but no differences in cardiac markers such as NTproBNP and troponin. In a multivariable model, LV hypertrophy (LV mass indexed, OR = 1.02 [1.00-1.03], p = 0.031), LV end-diastolic diameter (OR = 0.85 [0.74-0.98], p = 0.021) and LV end-systolic diameter (OR = 1.19 [1.03-1.349], p = 0.092) were predictive for VT occurrence with an area under the receiver operating characteristic of 0.76 [0.65-0.87].

Conclusions

The incidence of ventricular arrhythmia in wtATTR-CM is high and is associated with an advanced stage of left ventricular disease. Further studies are needed evaluating the role of VTs in predicting sudden cardiac death and the benefit of ICD therapy in wtATTR-CM.

SUBMITTER: Knoll K

PROVIDER: S-EPMC10380522 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy.

Knoll Katharina K Fuchs Patrick P Weidmann Isabel I Altunkas Fatih F Voss Stephanie S Lennerz Carsten C Kolb Christof C Kessler Thorsten T Schunkert Heribert H Reinhard Wibke W Groß Stefan S Trenkwalder Teresa T

Journal of clinical medicine 20230711 14

<h4>Background</h4>Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular arrhythmias, particularly ventricular tachycardias (VTs), in wtATTR-CM is unclear. With the development of targeted therapies and improved overall prognosis, there is an unmet need to identify patients at high risk for VTs who might benefit from ICD therapy.<h4>Methods</h4>Between 2017 and 2022, 72 patients diagnos ...[more]

PMID: 37510739

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Project description:ImportanceTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.ObjectiveTo assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.Design, setting, and participantsThis retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024.Main outcomes and measuresThe primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR >20%).ResultsAmong 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was -5 mlL/min/1.73 m2 (-12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; P < .001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; P < .001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; P < .001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m2 [51-77] vs 61 mL/min/1.73 m2 [49-77]; P = .41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; P < .001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (P for interaction = .93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (P for interaction = .97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; P < .001).Conclusions and relevanceIn this retrospective cohort study, decline in kidney function was frequent in patients with ATTR-CM and was consistently associated with an increased risk of mortality, even after adjusting for established markers of worsening ATTR-CM. eGFR decline represents an independent marker of ATTR-CM disease progression that could guide treatment optimization in clinical practice.

Project description:BackgroundThe extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome.MethodsConsecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality.ResultsAmong 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively).ConclusionsDiffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis.

Project description:AimsRecognition of transthyretin amyloid cardiomyopathy is increasing due to advances in cardiac imaging and diagnostic strategies, but questions remain regarding disease frequency and characteristics. We examined the prevalence and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy of unascertained aetiology.Methods and resultsTTRACK was a multicentre, non-interventional, cross-sectional epidemiologic study funded by Pfizer and conducted in 20 hospitals and medical centres in 11 countries (NCT03842163). Eligible patients were aged ≥50 years, had hypertrophic cardiomyopathy (maximal end-diastolic left ventricular wall thickness ≥15 mm on echocardiogram) without an identified genetic or alternative origin at study enrolment, and underwent 99mTechnetium bone scintigraphy, with or without single photon emission computed tomography (SPECT). Cardiac-versus-bone uptake on scans was visually scored from 0 to 3 (Perugini scoring). Patients with grades 1-3 underwent monoclonal protein and laboratory testing and transthyretin (TTR) gene sequencing. Of 766 eligible patients, 691 (90.2%) had scintigraphy alone and 75 (9.8%) scintigraphy plus SPECT. Two hundred and eight patients (27.2%) had grade 2 or 3 cardiac uptake on scintigraphy; 144 (18.8%) had grade 2 or 3 cardiac uptake and no evidence of plasma cell dyscrasia and were diagnosed with transthyretin amyloid cardiomyopathy. Of patients with transthyretin amyloid cardiomyopathy, 11 (7.6%) had a pathogenic TTR gene variant and 34 (23.8%), 74 (51.7%), and 35 (24.5%) had New York Heart Association class I, II, and III/IV heart failure (HF) symptoms, respectively. Clinical and laboratory diagnostic characteristics were observed in ≥90% of patients with transthyretin amyloid cardiomyopathy. The characteristics most strongly associated with transthyretin amyloid cardiomyopathy on multivariable analysis were carpal tunnel syndrome (odds ratio [OR] 54.3; P < 0.0001) and male sex (OR 7.9; P < 0.0001).ConclusionsIn the TTRACK study, almost one in five patients ≥50 years of age with hypertrophic cardiomyopathy had transthyretin amyloid cardiomyopathy. Greater awareness of the frequency and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy are needed to help improve early detection of this debilitating but treatable disease.

Project description:AimsTo clarify the usefulness of left atrial (LA) function and left ventricular (LV) function obtained by two-dimensional (2D) speckle tracking echocardiography to diagnose concomitant transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with aortic stenosis (AS).Methods and resultsWe analysed 72 consecutive patients with moderate to severe AS who underwent 99m Tc-pyrophosphate (PYP) scintigraphy at Kumamoto University Hospital from January 2012 to September 2020. We divided these 72 patients into 2 groups based on their 99m Tc-PYP scintigraphy positivity or negativity. Among 72 patients, 16 patients (22%) were positive, and 56 patients (78%) were negative for 99m Tc-PYP scintigraphy. In clinical baseline characteristics, natural logarithm troponin T was significantly higher in the 99m Tc-PYP scintigraphy-positive than scintigraphy-negative group (-2.9 ± 0.5 vs. -3.5 ± 0.8 ng/mL, P < 0.05). In conventional echocardiography, the severity of AS was not significantly different between these two groups. In 2D speckle tracking echocardiography, the relative apical longitudinal strain (LS) index (RapLSI) [apical LS/ (basal LS + mid LS)] was significantly higher (1.09 ± 0.49 vs. 0.78 ± 0.23, P < 0.05) and the peak longitudinal strain rate (LSR) in LA was significantly lower in the 99m Tc-PYP scintigraphy-positive than scintigraphy-negative group (0.36 ± 0.14 vs. 0.55 ± 0.20 s-1 , P < 0.05). Multivariable logistic analysis revealed the peak LSR in LA and RapLSI were significantly associated with 99m Tc-PYP scintigraphy positivity. Receiver operating characteristic analysis showed that the area under the curve (AUC) of the peak LSR in LA for 99m Tc-PYP scintigraphy positivity was 0.79 and that the best cut-off value of the peak LSR in LA was 0.47 s-1 (sensitivity: 78.6% and specificity: 72.3%). The AUC of RapLSI for 99m Tc-PYP scintigraphy positivity was 0.69, and the cut-off value of RapLSI was decided as 1.00 (sensitivity: 43.8% and specificity: 87.5%) according to the previous report. The 99m Tc-PYP scintigraphy positivity in patients with RapLSI ≥ 1.0 and the peak LSR in LA ≤ 0.47 s-1 was 83.3% (5/6), and the 99m Tc-PYP scintigraphy negativity in patients with RapLSI < 1.0 and the peak LSR in LA > 0.47 s-1 was 96.6% (28/29).ConclusionsLeft atrial and LV strain analysis were significantly associated with 99m Tc-PYP scintigraphy positivity in ATTR-CM patients with moderate to severe AS. The combination of the peak LSR in LA and RapLSI might be a useful predictor of the presence of ATTR-CM in patients with moderate to severe AS.

Dataset Information

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy.

Background

Methods

Results

Conclusions

Publications

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy.

Similar Datasets

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