Relation Between Native AV Opening During Exercise and Development of AI
All seven patients in the opening AV group did not experience AI at 6 months. Of the remaining 30 patients in the closed AV group, 13 developed AI (43%) (Figure 2).
Preoperative Predictors of Native AV Opening During Exercise
Among the preoperative parameters, the lower cumulative dose of carvedilol was the only significant predictor of native AV opening during exercise (p < 0.05) (Table 3).
Preoperative Predictors of AI-Free Status Among Those With Closed AV
Among the remaining 30 patients with a closed AV, logistic regression analyses revealed that the use of the centrifugal pump was the only significant predictor of AI-free status (p = 0.036 and odds ratio, 5.400) (Table 4).
Prognosis and Native AV Opening During Exercise
The opening AV group had a higher readmission-free ratio because of cardiovascular events including cerebrovascular thrombosis, heart failure, and ventricular tachyarrhythmia (100% vs. 56%, p = 0.005; Figure 3A) or survival (100% vs. 84%, p = 0.308; Figure 3B) compared with the closed AV group during the postoperative 2 years study period.
Cox regression analyses showed a significant predictability of AV opening for readmission-free rate (p = 0.048; hazard ratio, 0.018), whereas younger age was not a significant predictor (p = 0.241).
We demonstrated here that 1) some patients could achieve native AV opening during exercise at 3 months although their native AV remained closed at rest, 2) these patients had better exercise tolerability and more improved LV contractility during exercise compared with the closed AV group, 3) no patients in the opening AV group experienced AI development at 6 months, and 4) these patients had a higher readmission-free ratio because of cardiovascular events during the 2 years CF LVAD treatment.
Clinical Evil of AI Development in the Era of Long-Term CF LVAD Treatment
Aortic insufficiency remains one of the unsolved concerns even in the era of CF LVAD because it reduces systemic circulation and increases intracardiac pressure.3 Clinically, AI facilitates congestive symptoms, ventricular tachyarrhythmia, and dyspnea on effort and may reduce patients’ quality of life or survival.2,5,7,10
Despite the recently proposed surgical interventions such as AV replacement or repair, no procedures with few complications have been established thus far.4 Therefore, optimal patient selection and a prophylactic strategy should be established to prevent the development of AI.
Here, we assessed AI at 6 months because we previously demonstrated that no de novo AI developed after 6 months,5 and some patients were eliminated because of death or transplant soon after the 6th month.
Opening of Native AV at Rest and Development of AI
The opening of native AV at rest is sufficient to prevent development of AI,2,6,7,10,11 probably because daily opening of native AV would avoid fusion of native AV, increase pulse pressure in the aortic root, and prevent degenerative remodeling of the aortic root.12–14
Opening of the native AV is achieved by sufficient recovery of LV contractility during LVAD support because intracardiac pressure in the systolic phase should exceed that of the aortic root to open the native AV.2 In this study, we assessed opening of the native AV at 3 months because LV reverse remodeling is accomplished by approximately the 3rd month after LVAD implantation.15
Opening of Native AV During Exercise and Development of AI
Among those with a closed AV at rest, approximately 20% of patients achieved opening of the native AV during exercise. To the best of our knowledge, this is the first study to discuss opening of the native AV during exercise under LVAD support.
The opening AV group had significantly improved LVEF during exercise, whereas these patients had a comparatively low LVEF at rest compared with the closed AV group. Such patients would have an LV contractile reserve.16 They also had a significantly greater improvement in exercise capacity, probably because of enhanced cardiac contractility during exercise. Younger patients had such a higher cardiac reserve. Young age may be an important factor for AV opening during exercise although it was not a significant predictor of the readmission-free ratio by Cox regression analyses.
Surprisingly, no patients in the opening AV group experienced AI (Figure 2). The native AV started opening soon after the initiation of CPXT. They will achieve native AV opening during light-labor activities in daily life. Echocardiography performed only at rest may not always be sufficient for assessing the cardiac condition including the opening of the native AV during daily living activities.
Insufficient preoperative β-blocker treatment was the only significant predictor of native AV opening during exercise. These patients have a higher possibility of being responders to β-blocker treatment under LVAD treatment because they have a lesser chance of undergoing trial β-blocker titration because of acute worsening of HF, as we have previously demonstrated.17
Among the remaining 30 patients with a closed AV, 17 were able to avoid AI development. Logistic regression analyses revealed that use of the centrifugal pump was the only preoperative predictor of AI-free status in this population. Those receiving centrifugal LVAD have higher pulse pressure compared with those receiving the axial type. Preserved pulse pressure prevents both remodeling of the aortic root and degeneration of AV, which facilitates the development of AI.5 Therefore, use of the centrifugal pump would be another factor that prevented AI.
Clinical Impact of Opening of Native AV During Exercise
Patients in the opening AV group had a higher readmission-free ratio because of cardiovascular events compared with those in the closed AV group (Figure 3). They were free from AI, which would increase intracardiac pressure because of a retrograde flow through the native AV that facilitates congestion and ventricular tachyarrhythmia. Forward flow through the native AV, probably observed during daily activity, would reduce the formation of turbulence and a thrombus in the aortic root, which may prevent occurrence of fatal cerebrovascular thrombosis.5,18 Those with the opening AV were younger, but young age was not found to be a significant predictor of the readmission-free rate.
Intervention for Facilitating Opening of Native AV
There has been no established strategy to facilitate the opening of the native AV and prevent development of AI thus far.
Native AV has a tendency toward opening under a lower rotation speed,11 but the cardiac output is often decreased to a lower level, which is required by the patients for daily living activities. Three-fifths of patients who received Jarvik 2000, which has an intermittent lower speed mode, experienced AI. Adjustment of rotation speed may be insufficient to open the native AV.
Aggressive cardiac rehabilitation, as recommended in the 2013 International Society of Heart and Lung Transplantation (ISHLT) guidelines improves exercise tolerability and contractile reserve,19 which may facilitate opening of the native AV during daily activity as seen in our results. However, implementation of a specific rehabilitation program to open the native AV would remain a future concern.
- The current study was performed retrospectively in a very small population in a single center. In the analysis using the unpaired t-test, the power was 0.5 with an effect size of 0.8 and error probability of 0.05. The results should be confirmed in a future multicenter large-scale study that includes prospective cardiac rehabilitation.
- All participants had preserved exercise tolerance and could undergo CPXT. Our result would not be adopted in those with low exercise tolerability. However, native AV would not open in patients who are sick. Opening of the AV is expected in those with sufficient exercise tolerability and cardiac reserve.
- We enrolled only five patients who were receiving Jarvik 2000. The advantage of its intermittent lower speed mode in facilitating opening of the native AV and preventing AI remains unconfirmed.
- We performed echocardiography at 3 and 6 months after LVAD implantation. Monthly procedures would have strengthened our results.
Opening of the native AV during exercise was sufficient to prevent the development of AI in patients with a closed native AV at rest. Aggressive cardiac rehabilitation to improve exercise tolerability may have a prophylactic impact on development of AI during CF LVAD treatment.
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Keywords:Copyright © 2015 by the American Society for Artificial Internal Organs
ventricular assist device; cardiopulmonary exercise; reverse remodeling; heart failure