ΓΙΩΡΓΟΣ ΜΑΚΑΒΟΣ, MD, PhD ΚΑΡΔΙΟΛΟΓΟΣ, ΕΠΙΜΕΛΗΤΗΣ Β Γ ΠΑΝΕΠΙΣΤΗΜΙΑΚΗ ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ Γ.Ν.Ν.Θ.Α. ΣΩΤΗΡΙΑ

ΓΙΩΡΓΟΣ ΜΑΚΑΒΟΣ, MD, PhD ΚΑΡΔΙΟΛΟΓΟΣ, ΕΠΙΜΕΛΗΤΗΣ Β Γ ΠΑΝΕΠΙΣΤΗΜΙΑΚΗ ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ Γ.Ν.Ν.Θ.Α. ΣΩΤΗΡΙΑ

Causes of TR Primary-Organic Secondary-Functional Rheumatic LV,valvular dysfunction I.Endocarditis Pulmonary hypertemdion Ebstein RV dysfunction Prolapse Carcinoid Congenital Papillary muscle dysfunction Connective tissue disease Τrauma Radiation Pacemaker/ICD

Tricuspid Valve Dysfunction Following Pacemaker or Cardioverter-Defibrillator Implantation In the USA, approximately 200,000 (600,000 worldwide) permanent pacemakers (PPMs) and 120,000 ICDs are implanted annually. The potential for cardiac implantable electronic device leads to interfere with TV function has gained increasing recognition as having hemodynamic and clinical consequences associated with incremental morbidity and death. The diagnosis and treatment of lead-related (as distinct from functional) tricuspid regurgitation pose unique challenges. A high level of clinical suspicion must be maintained to avoid overlooking the possibility that worsening heart failure is a consequence of mechanical interference with TV leaflet mobility or coaptation, as ICD recipients have, at baseline, LV systolic dysfunction and are thereby predisposed, independent of any effect of the device, to secondary or functional TR and right heart failure. Chang et al, J Am Coll Cardiol 2017;69:2331 41

Impact of Tricuspid Regurgitation on Long- Term Survival Increasing TR severity is associated with worse survival in regardless of LVEF or pulmonary artery pressure. Severe TR is associated with a poor prognosis, independent of age, biventricular systolic function, RV size, and dilation of the inferior vena cava. Nath et al. J Am Coll Cardiol 2004;43:405 9

TR and Mortality in Patients With Transvenous Pacemakers Among patients with a PPM lead, the presence of Severe TR was associated with increased mortality (adjusted hazard ratio 1.40) PPM leads are associated with higher risk of STR after adjustment for LV systolic/ diastolic function and PH; similarly to STR from other cardiac pathologies, PPM-related STR is associated with increased mortality. Delling et al. Am J Cardiol 2016;117:988-992

TR PATHOPHYSIOLOGY Tricuspid regurgitation RA pressure CVP RV volume overload Renal dyfunction Symptoms and signs of RV failure RV dysfunction Cardiac output TV dysfunction following CIED implantation can manifest clinically as rightsided heart failure secondary to TR (or less often to tricuspid stenosis) Or as left-sided heart failure when RV volume overload impairs LV filling by direct ventricular interaction through the interventricular septum

MECHANISMS OF LEAD-RELATED TV DYSFUNCTION Structural consequences include: Valve leaflets, papillary muscles or chordae tendineae damage during lead placement or manipulation (perforation. laceration, avulsion) Mechanical interference with normal leaflet mobility and coaptation (impingement) leaflet entrapment, subvalvular support structure entanglement, Endocarditis. Damage to the TV can occur during extraction of infected or malfunctioning leads. Long-term interaction between endocardial leads and leaflet or chordal structures can result in inflammatory and fibrotic response, resulting in the encapsulation, ensheathment, or entrapment of the lead with subsequent loss of leaflet mobility or coaptation

TV ANATOMY The tricuspid apparatus comprises a nonplanar elliptical annulus, 3 leaflets (anterior,posterior, and septal), chordae tendineae, 2-3 papillary muscles (anterior and posterior) carrying chordae to a single leaflet. Some of the TV chordae tendineae attach directly to the interventricular septum, RV free wall, or moderator band in the absence of an intervening papillary muscle

TRICUSPID VALVE ANATOMY AND PHYSIOLOGY The septal portion of the annulus subtends the right fibrous trigone and is supported by the cardiac skeleton the mural portion of the annulus subtends the RV free wall and is prone to elongate under a state of chronic pressure or volume overload, leading to annular dilation TR begetstr chronic volume overload, chamber and annular dilation, leaflet tethering, and loss of coaptation, which worsen the TR and create a vicious cycle. Particularly when left-sided cardiac dysfunction predisposing the patient to functional or secondary TR coexists, even a modest increment in TR associated with the presence of a CIED lead can, over time, result in severe TR and right-sided heart failure.

Tricuspid annular dialatation,papillary muscle tethering-pathophysiology Reverse remodelling of the RV may not occur. The flattening of the TV annulus may stretch papillary muscles When septum is hypokinetic, dyskinetic, or dilated, there can be a tethering effect on the TV through papillary muscles of the septal leaflet

Prevalence of PM-associated TR Estimates of the prevalence of significant TR (defined as 2/4) and incidence of TR worsening (by 1 or more grades) following CIED implantation vary from 10% to 39%, with most (but not all) studies attributing a higher incidence of worsening TR to ICD leads (implicating their greater thickness and stiffness) and with the presence of more than 1 RV leads Some 21.2% of patients with baseline mild TR or less developed abnormal TR (3.4% mild-moderate, 12.8% moderate, 1.1% moderate-severe, 3.9% severe) after implant. TR worsened by 1 grade or more after implant in 24.2% TR worsening was more common with ICDs than PPMs in patients with baseline mild TR or less. (32.4% vs. 20.1%; P <.05). Kim et al.j Am Soc Echocardiogr 2008;21:284 7. Chang et al, J Am Coll Cardiol 2017;69:2331 41

Prevalence of TR PM-associated Lin et al. J Am Coll Cardiol 2005;45:1672 5 In a series of 41 patients undergoing TV surgery for severe TR believed to be caused by a CIED lead, leaflet perforation in 7 patients, leaflet entanglement in 4, leaflet impingement in 16, leaflet adherence in 14. The septal leaflet was most often (6 of 7 patients) perforated Postmortem analyses have also shown that TV lacerations are more common on the posterior leaflet

Lead related and TV endocarditis PM/ICD infection almost always necessitates lead extraction. Morbidity and mortality rates related to CIED infection increase significantly when the TV is involved compared with when evidence of TV endocarditis is absent. Patients undergoing removal of an infected device during hospitalization are one-half as likely to die (19.9%) at 1 year as patients who do not undergo device removal (38.2%) TV dysfunction in the setting of lead-related endocarditis can occur as a result of leaflet destruction by the infectious process itself or during lead extraction Predictors of TR worsening after TLE include removal of more than 1 lead, advanced age, and endocarditis involving the TV as the indication for device explantation Athan et al. JAMA 2012;307:1727 35. Coffey et al. Pacing Clin Electrophysiol 2014;37:19 24.

Pacemaker extraction Post endocarditis pre post

DIAGNOSIS OF TV DYSFUNCTION ASSOCIATED WITH PM/ICD LEADS 2D, 3D, and Doppler echocardiographic examinations are the mainstays for the diagnosis of TV dysfunction associated with CIED leads. The echocardiographic diagnosis of TR in patients with CIEDs is similar to that in patients without endocardial leads. ESC guidelines VHD 2017

PISA

Vena contracta

DIAGNOSIS OF TV DYSFUNCTION ASSOCIATED WITH CIED LEADS PM/ICD leads cause echocardiographic imaging artifacts and signal attenuation because of their high acoustic reflectivity, with underestimation of TR by Doppler color When TR is caused by an asymmetrical alteration in leaflet mobility, the regurgitant jet tends to assume an eccentric (wall-hugging), rather than a central, trajectory, resulting in loss of Doppler color flow signal (Coanda effect) and hence underestimation of regurgitation. In patients eventually found to have severe TR resulting from CIED leads, only 63% had a correct diagnosis by TTE during the preoperative study

DIAGNOSIS OF TV DYSFUNCTION ASSOCIATED WITH CIED LEADS Pattern of hepatic vein flow not affected by leadinduced acoustic artifacts. Holosystolic hepatic vein flow reversal is diagnostic of severe TR, although if the right atrium is severely dilated, the negative predictive value of hepatic vein systolic flow reversal may be reduced.

3D ECHO TV

Cheng et al. Echocardiography.2016;33:1689 96. Seo et al. Circ J 2008;72:1465 70. DIAGNOSIS OF TV DYSFUNCTION ASSOCIATED WITH CIED LEADS Sensitivity of 2D TTE for identification of a CIED lead as the primary cause of TV dysfunction is low (12% to 17%) 3D echocardiography offers improved spatial definition of the interaction between lead and valve or subvalvular apparatus 3D TTE was able to delineate the course and position of leads in 153 of 207 (74%) patients, with a clear association between lead impingement and worsening TR after lead placement In a comparison of 2D and 3D TTE for the diagnosis of lead-related TR in 87 patients with CIEDs, it was found that 2D TTE satisfactorily delineated the spatial relationship between lead and valve in only 17.2% of patients, whereas 3D TTE did so in 94.2%

3D Echo Location of Implantable Device Leads and Mechanism of Associated TR 3D TTE clearly depicted lead position in 90% of patients. Leads interfering with normal leaflet mobility were associated with more TR than nonimpinging leads (vena contracta: median 0.62 cm [1st and 3rd quartiles: 0.51, 0.84 cm] vs. 0.27 cm [1st and 3rd quartiles: 0.00, 0.48 cm]; p < 0.001). MedirattaJ Am Coll Cardiol Img 2014;7:337 47

3D Echocardiographic Location of Implantable Device Leads and Mechanism of Associated TR An intercommissural or middle-of-the-annulus position is desired to minimize device-related TR post implantation 3D TTE showed a clear association between device lead position and TR. To minimize TR induced by device-leads, 3D TTE guidance should be considered for placement in a commissural position. MedirattaJ Am Coll Cardiol Img 2014;7:337 47

Impinging septal leaflet causing TR Non impinging

Impinging posterior leaflet

TREATMENT OF TV DYSFUNCTION ASSOCIATED WITH PM LEADS Valve repair: Suture (DeVega) annuloplasty, Ring annuloplasty Damage to the leaflets: suture or patch repair. The lead can be repositioned to prevent leaflet impingement by securing it in a location abutting the tricuspid annulus in a cleft created by suture bicuspidization of the valve. Valve replacement with or without lead retention. Lead extraction without valve repair or replacement, adequate to ameliorate lead related TR usually cannot be determined and depends on severity of RV and tricuspid annular dilation, the degree of leaflet tethering, and the extent of leaflet damage or distortion. If the lead is relatively new, with minimal leaflet damage or distortion, a surgical procedure may be avoided. Because further damage may ensue, a valve replacement or repair strategy must be in place before TLE. Nazmul et al. Europace 2013;15:409 13. Chang et al. J Am Coll Cardiol 2017;69:2331 41

INDICATIONS FOR REMOVAL OF LEADS TO TREAT TR TV repair or replacement for lead-related: no prospective data to support TR in the absence of device or endovascular infection as an indication for TLE Risk-benefit ratio incremental morbidity and mortality independently attributable to severe TR against those associated with lead removal with or without TV repair or replacement. The excess mortality rates associated with severe TR have been estimated to be 31% in the general population and 40% to 75% in patients with PM/ICDs.when operative risk is low, patients with leadrelated severe TR would be expected to benefit from corrective intervention. Patients with symptomatic severe TR and with compelling 3D echocardiographic evidence that valve function has been compromised primarily by the lead Likelihood of successful treatment by lead extraction and valve repair or replacement decreases with increasing duration of TR when the tricuspid annulus and RV are dilated that leaflet coaptation would not be possible even in the absence of the lead. Strategies to pace the heart without crossing the TV, and thus not interfering with its closing mechanism, include placement of a coronary sinus pacing lead, surgical epicardial placement of leads, and leadless pacing systems. Chang et al. J Am Coll Cardiol 2017;69:2331 41

ESC guidelines VHD 2017

CONCLUSIONS Although the putative contribution of PM/ICD leads to TV dysfunction has gained increasing recognition as having hemodynamic and clinical consequences associated with incremental morbidity and death, all evidence are from retrospective analyses. A higher level of clinical suspicion with 3D echocardiography, may alert the clinician to the possibility that worsening heart failure is consequence of mechanical interference with TV leaflet mobility or coaptation and is amenable to lead extraction or valve repair or replacement. When clinical, hemodynamic, and echo assessment provides compelling evidence of lead related severe TR, corrective intervention should be provided in a timely fashion, before the onset of severe annular and chamber dilation and severe RV dysfunction The future in which endocardial leads are absent or nontransvalvular is likely to be associated with a reduction in lead-related cardiac dysfunction.

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