Impact of fixed pulmonary hypertension on post–heart transplant outcomes in bridge-to-transplant patients

doi:10.1016/j.healun.2010.06.002

The Journal of Heart and Lung Transplantation

Volume 29, Issue 11, November 2010, Pages 1253-1258

https://doi.org/10.1016/j.healun.2010.06.002 Get rights and content

Background

Fixed pulmonary hypertension (FPH) is considered a contraindication to cardiac transplantation. Ventricular assist device (VAD) therapy through prolonged left ventricular unloading may reverse FPH. Our aim was to assess post-transplant outcomes and survival in patients with and without FPH undergoing VAD implantation as bridge to transplant.

Methods

Fifty-four patients received an intracorporeal left VAD (LVAD) as a bridge to transplant from 2000 to 2008 at two institutions (Rigshospitalet, Denmark, and the Toronto General Hospital, Canada). Twenty-two (41%) patients had fixed FPH (defined as pulmonary vascular resistance [PVR] >3 Wood units and resistant to pulmonary vasodilators) prior to VAD implant (FPH group) and were compared with 32 patients without FPH (NoFPH group). Baseline characteristics, pre- and post-transplant pulmonary pressures, incidence of complications and post-transplant survival were analyzed.

Results

Baseline characteristics were similar except that patients in the FPH group were older (46 ± 11 years vs 39 ± 13 years in the NoFPH group, p < 0.05). The mean pre-VAD PVR was 4.3 ± 1.7 Wood units in the FPH group and 1.7 ± 0.5 Wood units in the NoFPH group (p < 0.001). Pulmonary pressures were higher in the FPH group immediately prior to VAD implant, but they were comparable immediately pre-transplant and during the first year post-transplant. The incidence of post-transplant RV failure was not significantly different between groups. Post-transplant survival was similar between groups.

Conclusions

VAD therapy successfully decreases pulmonary hypertension, even in patients with “fixed” FPH, allowing candidacy for heart transplantation. Among bridge-to-transplant candidates, the presence of FPH does not reduce post-transplant survival.

Section snippets

Patient population

This is a retrospective cohort study that included 54 patients undergoing VAD implantation as a bridge to transplantation from 1999 to 2008 at two institutions (Rigshospitalet, Denmark, and the Toronto General Hospital, Canada). The devices utilized were the HeartMate XVE, the HeartMate II (Thoratec Corp., Pleasanton, CA) and the Novacor (World Heart Corp., Oakland, CA). Patients were divided in two groups according to the presence or absence of FPH prior to VAD implantation. Twenty-two (41%)

Baseline characteristics

A total of 54 patients were included in this study. The median overall age was 44.5 years (range 17 to 63 years) and 90% (46 patients) were male. The median follow-up was 2.8 years. Pulmonary hypertension was present in 41% (22 patients) of the population. Baseline characteristics (Table 1) were similar among patients with and without FPH, except that patients in the FPH group were older (46 ± 11 years vs 39 ± 13 years in NoFPH group, p < 0.05) and showed a trend toward higher incidence of

Discussion

This study has shown that VAD therapy decreases FPH in advanced heart failure patients, allowing them to safely undergo heart transplantation. In addition, among heart transplant candidates supported with a VAD, long-term post-transplant survival in patients with FPH is comparable to that of patients without FPH.

Pulmonary hypertension is a common complication of severe chronic heart failure that may preclude cardiac transplantation. Moderate to severe FPH (>2.5 Wood units) is present in

Disclosure statement

The authors have no conflicts of interests to disclose.

References (22)

J.M. Chen et al.
Reevaluating the significance of pulmonary hypertension before cardiac transplantation: determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality
J Thorac Cardiovasc Surg
(1997)
J. Butler et al.
Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation
J Heart Lung Transplant
(2005)
J.F. Delgado et al.
Impact of mild pulmonary hypertension on mortality and pulmonary artery pressure profile after heart transplantation
J Heart Lung Transplant
(2001)
M.R. Mehra et al.
Lisitng criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006
J Heart Lung Transplant
(2006)
B. Stobierska-Dzierzek et al.
The evolving management of acute right-sided heart failure in cardiac transplant recipients
J Am Coll Cardiol
(2001)
D. Zimpfer et al.
Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates
J Thorac Cardiovasc Surg
(2007)
O.H. Frazier et al.
Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation
J Thorac Cardiovasc Surg
(2001)
S.G. Drakos et al.
Effect of mechanical circulatory support on outcomes after heart transplantation
J Heart Lung Transplant
(2006)
V. Patlolla et al.
The effect of ventricular assist devices on post-transplant mortality: an analysis of the United Network for Organ Sharing Thoracic Registry
J Am Coll Cardiol
(2009)
J.C. Matthews et al.
The right ventricular heart failure risk scoreA pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates
J Am Coll Cardiol
(2008)

J. Butler et al.

Pulmonary hypertension and exercise intolerance in patients with heart failure

J Am Coll Cardiol

(1999)

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Citation Excerpt :
Severe fixed PH and elevated pulmonary vascular resistance (PVR) are considered relative contraindications for HT due to increased right ventricular (RV) dysfunction and mortality posttransplant.1,2 In this patient population, left ventricular assist devices (LVADs) have been used successfully to reverse “fixed” PH when used as a bridge to HT, with good outcomes.3,4 The off-label use of sildenafil, a phosphodiesterase-5 inhibitor, recently has been studied in an attempt to more noninvasively reduce pulmonary artery pressures.5
This special article focuses on the highlights in the cardiac transplantation literature in the year 2020. These include the selection and optimization of both the recipient and donor organs, including the use of prehabilitation, the use of new bridging techniques, the use and outcomes of using mechanical circulatory support, including left ventricular assist devices and the total artificial heart, the effects of the COVID-19 pandemic in previously transplanted patients and transplant candidates, and updates the perioperative management of this patient population.
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Left ventricular assist devices (LVAD) are increasingly implanted in advanced heart failure patients to improve survival and quality of life either as a bridge to transplant, bridge to recovery or as destination therapy. LVAD therapy is often accompanied by a profound lowering of pulmonary artery pressure due to mechanical unloading of the left ventricle. Persistent pulmonary hypertension (PH) after LVAD implantation increases the risk of right ventricular failure (RVF). In this context pulmonary vasodilators have been implemented: a) as a strategy to reduce afterload and wean patients with RVF from inotropes in the early postoperative period, b) as long-term therapy aiming to optimize right heart hemodynamics and prevent late RVF and c) in order to lower persistently elevated pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) after LVAD and enable candidacy for heart transplantation. However, considerable uncertainty exists regarding the risks and benefits of these strategies and practices vary widely among institutions. This article provides an overview of the available evidence and existing recommendations regarding the use of pulmonary vasodilators in LVAD recipients.
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Although extremely high pulmonary vascular resistance (PVR) is a relative contraindication for heart transplantation (HTx), recent data with continuous-flow left ventricular assist devices (LVADs) indicate HTx outcomes may be different when high PVR is managed with an LVAD. This study clarifies the contemporary association between PVR at HTx and posttransplant survival in LVAD vs non-LVAD cohorts.
We reviewed the United Network for Organ Sharing registry for adults who received a transplant from 2008 to 2015. In those with continuous-flow LVADs and those with no VADs at HTx, (non-VAD), we grouped patients by low PVR (PVR <3), intermediate PVR (PVR 3 to <6), and high PVR (PVR ≥6) groups. Adjusted hazard ratios (aHRs) for death after HTx were calculated by Cox regression.
The non-LVAD cohort included 6270 patients (4385 in low, 1643 in intermediate, and 242 in high PVR), and the LVAD cohort included 4111 patients (3227 in low, 798 in intermediate, and 86 in high PVR). The high PVR LVAD group had the worst survival, which was not significant, likely to low power (P = .300). The aHR for death in non-LVAD was 1.047 (95% confidence interval, 1.010-1.088) and in LVAD was 1.063 (95% confidence interval, 1.010-1.119). Cubic spline analysis demonstrated nonlinear associations between PVR and the aHR, especially in the LVAD cohort.
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Original clinical scienceImpact of fixed pulmonary hypertension on post–heart transplant outcomes in bridge-to-transplant patients

Background

Methods

Results

Conclusions

Section snippets

Patient population

Baseline characteristics

Discussion

Disclosure statement

J Thorac Cardiovasc Surg

J Heart Lung Transplant

J Heart Lung Transplant

J Heart Lung Transplant

J Am Coll Cardiol

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Heart Lung Transplant

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Original clinical science
Impact of fixed pulmonary hypertension on post–heart transplant outcomes in bridge-to-transplant patients