Search

Background The incidence and risk factors of pacemaker (PM) implantation in patients with cardiac amyloidosis (CA) are largely unexplored. Purpose We sought to characterise the trends in the incidence of permanent PM and to identify baseline predictors of future PM implantation in light chain (AL) and transthyretin (ATTR) CA. Methods Multicentre, retrospective, observational study. Consecutive patients with AL and ATTR-CA diagnosed or referred at participating Centres between 2017 and 2020 were included. Clinical data recorded within ± 1 month from baseline evaluation were collected from electronic medical records. The primary outcome of the study was the need for clinically-indicated PM implantation. Reversible causes of conduction system disease were systematically ruled out before PM implantation. Patients with PM (n=41) and/or permanent defibrillator in situ (n=13) at the time of CA diagnosis were excluded. Results The study population consisted of 405 patients: 29.4% AL, 14.6% variant ATTR and 56% wild-type ATTR; 82.5% were males, with median age 76 years. During a median follow-up of 33 months (interquartile range 21–46), 36 (8.9%) patients experienced the primary outcome: 10 patients with AL-CA, 2 with variant ATTR-CA and 24 with wild-type ATTR-CA (p=0.08). At multivariable analysis, history of atrial fibrillation (hazard ratio [HR] 3.80, p=0.002), PR interval (HR 1.013, p=0.002) and QRS >120 ms (HR 4.7, p=0.001) on baseline ECG were independently associated with PM implantation (Figure 1). In the individual patient, the contemporary presence of these 3 factors yielded the highest risk of PM implantation (HR 6.26, p=0.003). Conclusion In a large cohort of AL and ATTR-CA, the incidence of PM implantation was high accounting for ≈9% of patients in the 3 years following the diagnosis. History of atrial fibrillation, longer PR interval and QRS >120 ms identified CA patients at high-risk of future PM implantation (Figure 2). CA patients with these features might need close monitoring during follow-up for the development of conduction system disease requiring PM implantation. Funding Acknowledgement Type of funding sources: None.

Background Clinicians need to identify patients with amyloid cardiomyopathy (AC) at an early stage, due to the availability of disease–modifying therapies. Some echocardiographic findings may rise the suspicion of AC, also in patients with mild or no symptoms, addressing second level diagnostic tests. Aim To investigate the prevalence of AC in consecutive patients ≥55 years undergoing clinically indicated, routine transthoracic echocardiogram in Italy and presenting echocardiographic signs suggestive of AC. Methods This is a prospective multicentric study conducted in Italy. It comprises two phases: 1) a recording phase consisting in a national survey on prevalence of possible echocardiographic red flags of AC in consecutive unselected patients ≥55 years undergoing routine echocardiogram (previously published) and 2) an AC diagnostic phase involving a diagnostic work–up for AC to investigate AC prevalence among patients with at least one echocardiographic red flag (herein presented). Patients that in Phase 1 presented an “AC suggestive” echocardiogram (i.e., at least one red flag of AC in hypertrophic, non–dilated left ventricles with preserved ejection fraction) underwent clinical evaluation, blood and urine tests and scintigraphy with bone tracer. Diagnosis of transthyretin related–AC (ATTR–AC) was made in presence of grade 2–3 Perugini uptake at scintigraphy and absence of monoclonal protein. The study was registered at ClinicalTrials.gov (#NCT04738266). Results Of the 5315 screened echocardiograms, 381 exams (7.2%) were classified as “AC suggestive” and proceeded to Phase 2. 217 patients completed Phase 2 investigations. Main reasons for the 164 non–entering patients into Phase 2 were death (n = 49) and refusal to participate (n = 66). A final diagnosis of AC was made in 62 patients with an estimated prevalence of 28,6% (95% CI: 22,5%–34,7%). ATTR–AC was diagnosed in 51 and AL–AC in 11 patients, ascertaining a prevalence of 23,5% (95% CI: 17,8%–29,2%) and 5,1% (95% CI: 2,2%–8,0%), respectively. Conclusion Among a cohort of consecutive unselected patients ≥55 years with echocardiographic findings suggestive of AC, the prevalence of AC ranged from 23% up to 35%. Although ATTR–AC was predominant, AL–AC was diagnosed in a significant number of cases. Echocardiography has a fundamental role in screening patients, raising the suspicion of disease and orienting diagnostic work–up for AC.

The base 2-carbon of 2',3'-di-O-acetyl-2'-deoxyinosine is strongly activated towards nucleophillic attack when either the 4-nitrophenyl or 2,4-dinitrophenyl group is attached to its N-1 position (product 1 or 2), 1-(omega-Aminoalkyl)- and 1-(omega-hydroxyalkyl)-2'-deoxyinosine derivatives 5, 8-10 have been efficiently synthesized by a rearrangement of the purine ring upon treatment of compound 1 or 2 with the appropriate alpha,omega-diamine or alpha,omega-hydroxyamine. Moreover 1-amino-2'-deoxyinosine 11 and 1-hydroxy-2'-deoxyinosine 13 have been easily prepared in high yields by reaction of substrate 1 or 2, respectively with hydrazine or hydroxylamine.