Natural course and prognostic impact of lead-related tricuspid regurgitation
Authors: Gitto M , Fazzari F , Ferrante L , Del Monaco G , Donia D , Caracciolo A , Regazzoli D , Reimers B , Frontera A , Monti L , Mangieri A , Francone M , Lisi C , Colombo A , Sticchi A 
Published: November 2023

Abstract

Aim
Direct injury from Cardiac Implantable Electrical Device (CIED) leads is one of the most common causes of tricuspid regurgitation (TR), with a reported prevalence up to 40%. Little is known about the natural history of CIED-related TR and the prognostic impact of worsening TR detected at different time points after CIED implantation.

Methods
The CIED-IT registry retrospectively included patients who underwent CIED implantation in a tertiary referral center in Italy, as long as they had been performed repeated transthoracic echocardiograms (TTE) and at least one chest CT after the implantation. TR severity was graded using a pre-specified 4-class grading scheme: mild, moderate, severe and massive. The primary endpoint for outcome analysis was major adverse clinical events (MACE), defined as the composite of all-cause death or heart failure (HF) hospitalizations.

Results
249 patients undergoing CIED implantation from January 2015 to December 2021 were included. Median time to last available TTE was 1593 days (IQR 857-2089). TR prevalence was 71.8% (178/248) at baseline and 88.7% (220/248, p&lt;0.001) at last available TTE. Worsening TR was observed in 48.4% (120/248) of cases.
Mean age was 74.5±10.1 years, 35% of patients were females, 45.6% had atrial fibrillation and 41.9% had a LVEF &lt;40%. Baseline RV dysfunction was present in 23.8% of patients, while a worsening RV function was observed in 24.2% of patients with worsening TR and 10.1% of those without worsening TR (p=0.003).
Median follow-up time was 4.2 years (IQR: 2.4-5.6). At Kaplan Maier analysis, the cumulative 5-year MACE incidence was 39.4% (95% CI: 30.4-50%) in patients with worsening TR and 18.9% (95% CI: 12.5-28.1%) in those with no worsening TR (Log-Rank p = 0.01). This difference was mainly driven by a higher rate of heart failure hospitalizations in the worsening TR group (36.5% vs, 10 at 5y, Log-Rank p&lt;0.001), while the rate of all-cause death was comparable between the two groups (Log-Rank p=0.313). At multivariable stepwise Cox regression analysis, worsening TR was an independent predictor of both MACE (HR 1.89, 95% CI: 1.15-3.11, p=0.012) and HF hospitalizations (HR 2.77, 95% CI: 1.49-5.16, p=0.001).
In a subgroup analysis including patients who also received a 1-year TTE (median time 182 days, IQR: 74-286), worsening TR at last available TTE was still an independent MACE predictor (HR 1.75, 95% CI: 1.0-3.1, p=0.05), while worsening TR at 1y was not (HR 1.66, 95% CI: 0.9-3.06).

Conclusions
CIED-related TR is a strong determinant of long-term adverse cardiovascular outcomes in patients undergoing CIED implantation. Lead-induced injury is sometimes not evident in the first months after the procedure and might require years to develop clinically significant TR. Serial echocardiographic assessments are therefore pivotal to implement risk stratification, while further knowledge of the pathophysiology of CIED-related TR is required to prevent its occurrence.Kaplan Maier Curves for MACEKaplan Maier curves for HHF