Abstract
Purpose: Despite their efficacy, LVADs remain associated with serious complications. The relationship between haemodynamic changes during support and outcome remains inadequately characterised. This association was investigated in LVAD recipients undergoing prolonged support.
Methods: Forty patients receiving LVAD therapy for >2 years were reviewed retrospectively (mean support duration was 38.62 ± 15.28). Pre- and on-LVAD haemodynamic data were assessed in three groups: (1) those receiving ongoing support (n = 24); (2) those who underwent cardiac transplantation (n = 4); (3) those who died during support (n = 12).
Results: For group 1 and 2, LVAD support achieved a decrease in mean PAP, mean PCWP, TPG, and PVR and an increase in thermodilution blood flow (TBF) with significance at ≤5% level. For group 3, there were non-significant changes in TPG and PVR at the 5% level but for mean PAP, mean PCWP, and TBF the changes were similar to Groups 1 and 2 with significance at ≤5% level. Aggregated data from all three groups showed a 58% increase in TBF on LVAD support.
Conclusion: Highly significant and favourable haemodynamic changes were found. However, group 3 did not undergo decrease in TPG and PVR possibly because of suboptimal LVAD flow, right heart dysfunction and unavoidable prolongation of support.
Keywords: LVAD, artificial heart, heart failure
Introduction
Although heart transplantation remains the gold standard for the treatment of end-stage heart failure with an average 2-year survival rate of 80%,1) its epidemiological impact is limited by organ availability.2) Over the last 5 years, rotary left ventricular assist devices (LVADs) have been used increasingly either as a bridge to transplant or for permanent support. In spite of their clinical efficacy, LVADs remain associated with serious complications which compromise outcome. However, the association between changes in haemodynamic parameters during support and outcome remains inadequately characterised. In this study, this association was investigated in LVAD recipients undergoing prolonged support.
Patients and Methods
Between April 2001 and October 2012, 150 patients received LVADs in our institution of whom 40 (26.67%), who were included in this review, remained on support for at least 2 years. Preoperative right heart catheter data were unavailable for 3 patients because of precipitous preoperative haemodynamic deterioration. Study patient demographics are presented in Table 1. Preoperative haemodynamic data from right heart catheterisation were compared with the most recent haemodynamic measurements recorded during LVAD support. Initially, data were analysed in aggregate. Subsequently, patients were grouped as follows: group 1, patients who remained on circulatory support (implant duration 25 to 83 months); group 2, patients who subsequently underwent heart transplant (implant duration 28 to 56 months); group 3, patients who died on support (implant duration 24 to 90 months). The haemodynamic parameters which were assessed were mean pulmonary artery pressure (PAP), mean pulmonary capillary wedge pressure (PCWP), trans-pulmonary pressure gradient (TPG), thermodilution-derived blood flow measured according to the Fick method (TBF) and pulmonary vascular resistance (PVR). Data distribution was assessed for normality using the Shapiro-Wilk W test. All parameters were normally distributed with the exception of pre-operative PVR. Consequently, the paired t-test was used to test for significant changes during LVAD support for all parameters except for PVR where the Wilcoxon signed-rank test was applied accordingly. ANOVA was applied for group comparison. Data are presented as mean ± standard deviation (SD). A survival curve is presented according to the Kaplan-Meier method for all study patients.
Table 1.
Patients demographics
| Variable | |
|---|---|
| Diagnosis | |
| Dilated Cardiomyopathy | 29 |
| Ischaemic Cardiomyopathy | 4 |
| Congenital | 2 |
| Other | 5 |
| Age (years) at implant | |
| Mean ± SD | 45.07 ± 12.43 |
| Range | 18–65 |
| Gender | |
| Male | 39 |
| Female | 1 |
| Duration of support (months) | |
| Mean ± SD | 38.62 ± 15.28 |
| Range | 24–90 |
| LVAD type | |
| Jarvik 2000 | 2 |
| Thoratec HeartMate II | 19 |
| HeartWare HVAD | 19 |
| Preoperative status | |
| LVEF <30% | 40 |
| Inotropes | 23 |
| IABP | 5 |
| Levitronix Centrimag | 3 |
| CRT-D | 30 |
| Postoperative issues | |
| RVAD (Levitronix Centrimag) | 5 patients |
| Driveline infection | 11 patients |
LVAD: left ventricular assist device; LVEF: left ventricular ejection fraction; IABP: intra-aortic balloon pump; CRT-D: cardiac resynchronization therapy; RVAD: right ventricular assist device
Results
Table 2 shows an aggregated analysis of the haemodynamic parameters of all study patients.
Table 2.
Analysis of haemodynamic parameters of all study patients
| Pre LVAD Insertion | Latest measurement on LVAD | P-value | |
|---|---|---|---|
| Mean PAP (mmHg) | 39.49 ± 8.29 | 19.78 ± 7.85 | P <0.001 |
| Mean PCWP (mmHg) | 27.84 ± 6.57 | 11.4 ± 6.61 | P <0.001 |
| TPG (mmHg) | 11.65 ± 5.23 | 8.38 ± 4.19 | P <0.01 |
| TBF (L/min) | 3.2 ± 0.78 | 5.06 ± 0.95 | P <0.001 |
| PVR (Wood Units) | 3.79 ± 1.86 | 1.76 ± 1.03 | P <0.001 |
LVAD: left ventricular assist device; PAP: pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; TPG: trans-pulmonary pressure gradient; TBF: thermodilution blood flow; PVR: pulmonary vascular resistance
Prolonged support was associated with highly significant decrease in mean PAP, mean PCWP, PVR (p <0.001) and TPG (p <0.01) and a significant increase (58%) in blood flow (TBF) with respect to pre-operative values. For groups 1 and 2, LVAD support was associated with a decrease in mean PAP, mean PCWP, TPG, and PVR and an increase in TBF all of which were significant at ≤5% level (Table 3). For group 3, there were non-significant changes in TPG and PVR at the 5% level but for mean PAP, mean PCWP, and TBF the changes were similar to groups 1 and 2 and were significant at ≤5% level.
Table 3.
Group analysis of haemodynamic parameters
| Group 1 Survivors (n = 22) | Group 2 Transplanted (n = 4) | Group 3 Deceased (n = 11) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Pre-LVAD | Latest measurement on LVAD support | P-value | Pre-LVAD | Latest measurement on LVAD support | P-value | Pre-LVAD | Latest measurement on LVAD support | P-value | |
| Mean PAP (mmHg) | 39.86 ± 7.02 | 16.14 ± 6.48 | P <0.001 | 37 ± 3.61 | 24 ± 1.73 | P <0.05 | 38.73 ± 11.52 | 26.09 ± 7.38 | P <0.05 |
| Mean PCWP (mmHg) | 28.27 ± 5.77 | 8.32 ± 5.15 | P <0.001 | 24.67 ± 1.53 | 18 ± 5.29 | P <0.1 | 27.64 ± 9.01 | 16.18 ± 5.91 | P <0.05 |
| TPG (mmHg) | 11.59 ± 5.36 | 7.82 ± 3.92 | P <0.01 | 12.33 ± 5.03 | 6 ± 4.36 | P <0.01 | 11.09 ± 5.45 | 9.91 ± 4.64 | Not significant |
| TBF (L/min) | 3.22 ± 0.82 | 5.23 ± 0.87 | P <0.001 | 3.33 ± 0.55 | 5.6 ± 1.02 | P <0.05 | 3.24 ± 0.77 | 4.65 ± 1.02 | P <0.01 |
| PVR (Wood Units) | 3.72 ± 1.71 | 1.55 ± 0.82 | P <0.001 | 3.92 ± 21 | 1.18 ± 0.92 | P <0.05 | 3.45 ± 1.73 | 2.28 ± 1.3 | Not significant |
LVAD: left ventricular assist device; PAP: pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; TPG: trans-pulmonary pressure gradient; TBF: thermodilution blood flow; PVR: pulmonary vascular resistance
In group 3, the cause of death during LVAD support was: stroke (2 pts), gastrointestinal bleeding (1 pt), pump thrombosis (2 pts), multi-organ failure following multiple aortic valve interventions (1 pt), end-stage renal failure (1 pt), and unknown (5 pts). Of the 24 patients who remained on support, 23 were on the transplant waiting list and one was suspended because of respiratory failure. Overall, 11 (29.7%) study patients experienced driveline infection.
A survival Kaplan-Meier curve is presented for all study patients in Fig. 1. The devices used are shown in Fig. 2.
Fig. 1.
Kaplan-Meier survival curve is presented for all study patients.
Fig. 2.
Left ventricular assist devices (LVADs) used: Jarvik 2000 (A); HeartMate II (B); HeartWare HVAD (C).
Discussion
Since the REMATCH Trial,3) the technological development from pulsatile to continuous flow ventricular assist devices has led to an increased survival of patients on prolonged circulatory support.1,4–6) Continuous flow LVADs have proven their reliability in relation to outcome following elective surgery in chronic heart failure patients before the onset of cardiogenic shock.7) In patients up to 70 years of age without cardiogenic shock, diabetes and renal failure, circulatory support with a continuous flow LVAD showed 1- and 2-year survival of 80% and 70%, which was comparable with heart transplantation.1,8) However, LVAD therapy remains limited by refractory complications such as driveline infection, pump thrombosis, bleeding, and mechanical durability with particular reference to the driveline, aortic regurgitation and right heart failure.
Until now, the association between changes in haemodynamics and outcome has been incompletely characterized. In this study, we investigated this relationship. This study has shown that a period of circulatory support between 3 and 5 years is now an achievable target. In addition, our longest survival patient was successfully supported by a Jarvik 2000 for 7.5 years (90 months) which substantiates a previous report.9) Analysis of aggregate study data showed that prolonged LVAD support is associated with substantial increase in blood flow (58%, p <0.01) which is slightly less than that observed in previous studies (70%–94% and 114% for LVAD and BiVAD respectively) and may reflect a trend towards LVAD implantation at an earlier stage of heart failure.10,11) The “step increase” in perfusion elicited by LVADs in this study was associated with significant haemodynamic benefits in terms of PAP, PCWP, TPG, PVR and TBF (p ≤0.01). Group analysis of data reveals similarities between groups 1 and 2 where a beneficial effect on PVR and TPG was observed during LVAD support as reported previously.12) In contrast, group 3 patients did not show a statistically significant reduction in TPG and PVR during LVAD support, reflecting irreversible pulmonary hypertension. Consequently, prolonged support was required but with increased risk of complications and subsequently fatal outcome. Our analysis revealed an overall general improvement of all haemodynamic variables when each group was considered individually. The findings associated with group 3 are particularly relevant to future clinical practice. Probably the main contributing factor to the development of right heart failure following LVAD insertion is the inability to consistently predict its occurrence.13) An empirical approach combined with measures aimed to avoid this complication14) remain the best we can offer at present. Preoperative high pulmonary artery pressure deserves LVAD insertion whereas high preoperative central venous pressure, tricuspid regurgitation, hepatomegaly and ascites are detrimental in relation to outcome.15) In our experience, milrinone and nitric oxide do play an important role in its management but their use remains limited in advanced right ventricular failure in chronic LVAD patients. RVAD insertion is helpful in the acute setting. Preoperative assessment remains critical. We do use TAPSE but RVSWI is currently argued as a better parameter.16) Whilst the reversibility of pulmonary hypertension during LVAD support is unpredictable, timely implantation is a key determinant of favourable outcome and cost-effectiveness.7,17) Improving clinical outcomes with current generation devices favour extending LVAD therapy to patients of INTERMACS profile 4 to 67,18) but this remains controversial because although the anticipated surgical risk should be lower with better survival, the haemodynamic benefit may be reduced. This issue should be addressed by the REVIVE-IT study where HeartMate II LVAD therapy outcomes will be compared with optimal medical treatment in patients with New York Heart Association (NYHA) Class III heart failure and should provide evidence for the extension of LVAD therapy beyond currently accepted criteria. At present, in the UK LVAD implantation is limited to heart transplant candidates and so non-transplant eligible patients who may be potential candidates for circulatory support are denied LVAD therapy. Aside from the need for a well-defined study to assess clinical and cost effectiveness in the context of destination therapy, ultimately the identification of suitable non transplant centres may help to address the treatment of the increasing number of patients with end-stage heart failure19) making LVAD therapy a potentially off-the-shelf solution for advanced heart failure.20)
Heart transplantation still remains the treatment of choice for patients with dilated cardiomyopathy and right ventricular dysfunction or young patients with complex congenital heart disease who have already undergone palliative surgery. However, given the significant shortage of suitable donors, it becomes imperative to find alternative solutions. LVAD therapy may well be the way forward and lead to a change in current terminology21) and more focus on heart failure surgery programs. This attitude may increase the number of referrals for LVAD therapy with potential increase in demand that may reduce the current cost of these devices. The development of totally implantable pumps powered by a trans-cutaneous external transmission system (TETS) technology with improved battery life is likely to make this therapy even more ergonomic and socially acceptable22,23) with the important benefit of eliminating abdominal driveline infection, which has been a significant limitation in our group of patients. In spite of the limitations of LVAD therapy, our analysis has shown consistent significant improvements in haemodynamic parameters in group I and group II during LVAD support. Therefore, LVADs have the capacity to restore an adequate cardiovascular status for patients bridged to transplant in a timely manner and for those who still remain on support a survival rate of 60% at three years is achievable.
Conclusion
The predominant findings were highly significant and favourable changes in haemodynamic parameters following prolonged LVAD support. However, patients who died during support were characterised by a sustained elevation of TPG and PVR. For this group, mortality risk was elevated possibly because of a trend to suboptimal LVAD flow, right heart dysfunction and unavoidable prolongation of support thereby increasing the exposure to the recognised risks of LVAD therapy. Although heart transplantation remains the definite treatment for heart failure at present, our data show that prolonged circulatory support is viable. Further improvements in outcome in this group are likely to occur as with technological advances in LVAD design.
Disclosure Statement
None.
References
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