Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation

Abstract

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease, in which atrial fibrillation (AF) has been shown to be prevalent. Cardiac scintigraphy with technetium-99m-pyrophosphate (99mTc-PyP) labeled bone-seeking tracers is used to noninvasively make the diagnosis of ATTR-CA, based on ventricular myocardial uptake. Assessment of atrial wall uptake (AU) on 99mTc-PyP is currently not used in the clinical setting Methods: We analyzed a cohort of patients referred for 99mTc-PyP scan at a tertiary center to explore AU and associations between any and incident AF, ATTR-CA, and all-cause mortality. Results: Among 580 patients included, 296 patients (51%) had a diagnosis of AF; 164 patients (28%) had scans consistent with ATTR-CA while 117 patients (20%) had AU. Of 117 patients with AU, 107 (91%) had any AF. In contrast, of 463 patients without AU 191(41%) had any AF. Of those with AU, 59/117(50%) patients had a 99mTc-PyP diagnosis of ATTR-CA while 58/117(50%) patients did not have such a diagnosis ( P =1.00). Patients with AU had significantly more any AF (hazard ratio [HR], 1.03 [95% CI, 1.02–1.04]; P <0.001), independent of ATTR-CA diagnosis and sex. On multivariable Cox proportional hazards analyses adjusting for age, AU, ATTR-CA diagnosis, sex, smoking, hypertension, diabetes, left ventricular ejection fraction, and coronary artery disease, both age (HR, 1.03 [95% CI, 1.02–1.04]; P <0.0001) and AU (HR, 2.68 [95% CI, 2.11–3.41]; P <0.0001) were independently associated with the development of any AF. Freedom from incident AF at 1-year was significantly lower in patients with AU, both in patients with and without ATTR-CA respectively (HR, 2.27 [95% CI, 1.37–3.78]; P <0.0001 versus HR, 2.21 [95% CI, 1.46–3.34]; P <0.0001). Conclusions: In a consecutive cohort of patients undergoing 99mTc-PyP scans, 20% had AU, which was statistically associated with any AF, independently of ATTR-CA diagnosis and sex. AU was associated with significantly lower freedom from incident AF at 1-year. Overlooking AU on 99mTc-PyP scans could potentially miss an earlier disease manifestation, or an additional risk factor for any/incident AF.

Transthyretin derived amyloid deposits in the atrium and the aortic valve: insights from multimodality evaluations and mid-term follow up

“…Di Bella et al reported in 2018 that atrial involvement in ATTR-CA is an early stage of ATTR-CA [ 7 ]. However, recent reports show contradictory results [ 2 , 4 ]. Ichimata et al [ 4 ], in line with Di Bella et al, reported in a study of 44 autopsy cases of ATTR-CA evaluating multiple cardiac regions that atria-predominant ATTR amyloid deposition may precede TTR amyloidosis of the ventricles; however, by using cluster analysis from retrospective insights.…”

Letter by Porcari et al Regarding Article, “Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation”

“…It is unclear whether patients underwent a comprehensive diagnostic work-up for ATTR-CM, as recommended by international societies of cardiology, 4,5 and how the disease was ruled out in challenging cases. Hussain et al 1 considered a heart-to-contralateral ratio >1.3 to indicate ATTR-CM. However, Perugini grade is the only validated scintigraphic scale through which this diagnosis can be established.…”

“…Hussain et al 1 report the results of a single-center retrospective analysis investigating the presence of atrial uptake (AU) of technetium-99m-pyrophosphate ( 99m Tc-PYP) and its association with atrial fibrillation (AF) in patients referred for suspected transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM). The authors found a 20% prevalence of AU on single-photon emission computed tomography (SPECT/CT) imaging that was associated with any AF and with significantly lower freedom from incident AF at 1-year, independently of ATTR-CM diagnosis and sex.…”

Response by Hussain et al to Letter Regarding Article, “Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation”

“…Other groups have also published that early and limited phenotypes of ATTR-CA may preferentially involve the atria for some (not all) patients. 2 Hence the importance of the central message in our article namely “that we can detect AU using cardiac scintigraphy with technetium-99 m-pyrophosphate and that this uptake is related to presence/absence of atrial fibrillation.” 3…”

“…2 Hence the importance of the central message in our article namely "that we can detect AU using cardiac scintigraphy with technetium-99 m-pyrophosphate and that this uptake is related to presence/absence of atrial fibrillation. " 3…”