Tricuspid Regurgitation After Heart Transplantation: The Cause or the Result of Graft Dysfunction?

BACKGROUND: Tricuspid regurgitation (TR) is common following heart transplantation and has been shown to adversely influence patient outcomes. The aim of this study was to identify causes of progression to moderate-severe TR in the first 2 y after transplantation. METHODS: This was a retrospective, single-center study of all patients who underwent heart transplantation over a 6-y period. Transthoracic echocardiogram (TTE) was performed at month 0, between 6 and 12 mo, and 1-2 y postoperatively to determine the presence and severity of TR. RESULTS: A total of 163 patients were included, of whom 142 underwent TTE before first endomyocardial biopsy. At month 0, 127 (78%) patients had nil-mild TR before first biopsy, whereas 36 (22%) had moderate-severe TR. In patients with nil-mild TR, 9 (7%) progressed to moderate-severe TR by 6 mo and 1 underwent tricuspid valve (TV) surgery. Of patients with moderate-severe TR before first biopsy, by 2 y, 3 had undergone TV surgery. The use of postoperative extracorporeal membrane oxygenation (ECMO) in the latter group was significant (78%; P < 0.05) as was rejection profile ( P = 0.02). Patients with late progressive moderate-severe TR had a significantly higher 2-y mortality than those who had moderate-severe TR immediately. CONCLUSIONS: Overall, our study has shown that in the 2 main groups of interest (early moderate-severe TR and progression from nil-mild to moderate-severe TR), TR is more likely to be the result of significant underling graft dysfunction rather than the cause of it.

Peri-procedural management of transcatheter mitral valve replacement in patients with heart failure.

Over the past decade, transcatheter mitral valve replacement (TMVR) technologies have evolved with the objective of improving outcomes for patients with severe mitral regurgitation (MR) deemed unsuitable for conventional mitral valve surgery. Although the safety and efficacy of transcatheter edge-to-edge mitral valve repair (TEER) is well-established, there is a sense amongst innovators that a major advantage of TMVR may be to offer a more complete solution for the correction of MR in patients whose complex anatomy means that the likelihood of achieving grade 0 or 1 MR with TEER is low. However, abrupt correction of MR in a poorly prepared left ventricle poses a number of unique haemodynamic challenges, particularly when sudden elimination of regurgitant flow causes a relative increase in left ventricular (LV) afterload. Rapid reduction in LV cavity size following MR elimination may itself result in relative LV outflow tract obstruction (LVOTO), irrespective of the intrinsic risk of LVOTO associated with TMVR. Nevertheless, TMVR on a beating heart affords the opportunity to study real-time invasive cardiac indices in high-risk patients with acute reversal of severe MR.

Improved right ventricular function following transapical transcatheter mitral valve implantation for severe mitral regurgitation.

BACKGROUND: Transapical transcatheter mitral valve implantation (TMVI) may be a therapeutic option for patients with severe mitral regurgitation (MR) excluded from cardiac surgery due to excessive risk. Exclusion criteria frequently include pulmonary hypertension and right ventricular (RV) dysfunction. The effect of TMVI on RV function has not previously been well-characterized. The aim of this study was to examine the procedural and 3-month impact of TMVI on RV hemodynamics and function. METHODS: This was a multi-center, retrospective, observational cohort study of patients with >3+MR undergoing TMVI. Pre- and post-TMVI hemodynamics were assessed with right heart catheterization. RV function was assessed at baseline, pre-discharge and at 3-months by echocardiography. RESULTS: Forty-six patients (age 72±9 years; 34 men) with ≥3+MR underwent TMVI over a 5-year period. Successful device implantation was achieved in all patients with abolition of MR (p < 0.001) and reduction in left-ventricular end-diastolic volume (p = 0.001). RV stroke work index (RVSWI) increased intra-operatively (7 ± 4 g/m/beat/m2 vs 11 ± 5 g/m/beat/m2; p < 0.001). At 3-months there were reductions in severity of tricuspid regurgitation (TR) (p < 0.001) and pulmonary artery systolic pressure (PASP) (49 ± 16 mmHg vs 36 ± 12 mmHg; p < 0.001), and improvements in RV fractional area change (28 ± 7% vs 34 ± 9%, p<0.001), tricuspid annular plane systolic excursion (TAPSE) (1.0 ± 0.3 vs 1.5 ± 0.5cm, p = 0.03), and RV free wall longitudinal strain (-14.2±5.0 vs -17.6±7.3, p = 0.05). CONCLUSIONS: Transapical TMVI results in significant improvement of RV function that is sustained to 3-months as evidenced by improvements in RVSWI and RV fractional area change, as well as reductions in PASP and TR severity.

Effects of modest iron loading on iron indices in healthy individuals.

Intravenous iron administration is typically indicated in individuals who have iron deficiency refractory to oral iron. However, in certain chronic disease states such as heart failure, it may be beneficial to administer intravenous iron to individuals who are not strictly iron deficient. The purpose of this study was to define a dose-response relationship between clinical indices of iron status and modest loading with intravenous iron in healthy, iron-replete participants. This was a double-blind, controlled study involving 18 male participants. Participants were block-randomized 2:1 to the iron and saline (control) groups. Participants in the iron group received 3.75 mg/kg body wt up to a maximum of 250 mg of intravenous iron, once a month for 6 mo, provided that their ferritin remained measured <300 µg/l within the week before a dose was due and their transferrin saturation remained <45%. Otherwise they received a saline infusion, as did the control participants. Iron indices were measured monthly during the study. The pulmonary vascular response to sustained hypoxia and total hemoglobin mass were measured before, at 3 mo (hemoglobin mass only), and at 6 mo as variables that may be affected by iron loading. Serum ferritin was robustly elevated by intravenous iron by 0.21 µg·l-1·mg-1 of iron delivered (95% confidence interval: 0.15-0.26 µg·l-1·mg-1), but the effects on all other iron indices did not reach statistical significance. The pulmonary vascular response to sustained hypoxia was significantly suppressed by iron loading at 6 mo, but the hemoglobin mass was unaffected. We conclude that the robust effect on ferritin provides a quantitative measure for the degree of iron loading in iron-replete individuals.NEW & NOTEWORTHY There has been an increasing interest in administering intravenous iron to patients to alter their iron status. Here, we explore various indices of iron loading and show that in healthy volunteers serum ferritin provides a robust indicator of the amount of iron loaded, with a value of 21 µg/l increase in ferritin per 100 mg of iron loaded.

Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P < 0.001). Following administration of intravenous iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P < 0.001, P < 0.005, and P < 0.001, respectively), and values for transferrin concentration fell significantly (P < 0.001). These changes remained significant at day 43 We conclude that the attenuation of the pulmonary vascular response to hypoxia by elevation of iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.