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Reverse Ramp Testing in Left Ventricular Assist Device Support and Myocardial Recovery

Holzhauser, Luise; Lang, Roberto M.; Raikhelkar, Jayant; Sayer, Gabriel; Uriel, Nir

Author Information
doi: 10.1097/MAT.0000000000001010

Abstract

Unloading of the failing heart with left ventricular assist device (LVAD) support can lead to clinically meaningful reversal of stress-related compensatory mechanisms.1

Bridge-to-recovery (BTR) studies have revealed large differences in the rate of ventricular recovery leading to device explantation ranging from 4.5% to 73%. The large differences in recovery rates are likely a result from the veracity with which “recovery” is screened for and the included patient population with respect to the etiology and duration of heart failure as well as patient’s age and sex.2

Recently published data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) reported a rate of recovery of 1.4% for all comers and 11.2% for patients with an a priori BTR strategy.3 One-year survival after LVAD explantation, available in INTERMACS for 21 (11%) patients, was 86%.3

We routinely strive for hemodynamic optimization in all our LVAD patients and have recently shown improved outcomes with this approach.4 Patients with potential for recovery are not managed differently. However, the identification of those patients with ventricular recovery who could be candidates for successful LVAD explantation remains challenging. Here we present a transthoracic echo (TTE) and right heart catheterization (RHC)-based protocol, which can be used to assess myocardial recovery, referred to as the “reverse ramp test.” The reverse ramp test allows for echocardiographic and hemodynamic assessment of the loaded left ventricle, which we believe is a valuable asset to routine testing for recovery.

Patient Selection

Reverse ramp testing can be considered as an adjunct to clinical decision making in medically optimized patients with BTR in whom myocardial recovery is suspected or in patients with a bridge-to-decision strategy to determine future trajectories.

We routinely perform the reverse ramp test at 6–12 months post-LVAD implantation in patients <50 years of age and short duration of heart failure <2–5 years.

We believe that along with goal-directed medical therapy, the first step toward higher rates of successful bridging to recovery is to actively screen for potential recovery. The LVAD reverse ramp protocol introduces a standardized and reproducible approach to screening for recovery, which could raise awareness and thus detection of recovery.

Here we report our experience in a highly selected group of seven LVAD patients, who were considered for LVAD decommissioning.

Preparation

The reverse ramp test requires device speed reduction to minimal settings, which requires anticoagulation with an international normalized ratio goal of 2–3.5 to limit the risk of device thrombosis.

Conduction of Left Ventricular Assist Device Reverse Ramp Testing

Transthoracic echo and hemodynamic parameters derived from RHC are assessed at baseline and at every LVAD speed turn down step during the protocol.

  • Transthoracic echo parameters: left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), aortic valve opening, degree of aortic insufficiency, and mitral regurgitation (MR)
  • Hemodynamic parameters: central venous pressure (CVP); systolic, diastolic and mean pulmonary artery pressure (PAP); pulmonary capillary wedge pressure (PCWP); pulmonary artery saturation; cardiac output (CO); and cardiac index (CI)
  • Pump parameters:
    • HeartMate II (HM II, Abbott, Chicago, IL) and HeartMate 3 (HM3, Abbott, Chicago, IL): speed, pulsatility index (PI), flow, power
    • HeartWare HVAD (HeartWare Inc., Framingham, MA): speed, upper flow (UF), lower flow (LF), average flow, power

For the HM II, the study starts at 8,000 rpm, and the speed is then decreased every 3 minutes by 400 rpm until the final stage at 6,000 rpm.

For the HM3, initial step is 5,000 rpm, and the speed is reduced by 100 rpm every 3 minutes to a final speed of 4,000 rpm.

For HVAD, the initial step is at 2,400 rpm, and the speed is reduced every 3 minutes by 100 rpm to a final speed of 1,800 rpm. At the last down step, patients are observed for 15 minutes. The reverse ramp protocols for HeartMate3, HeartMateII, and HVAD can be found in the appendix of this manuscript (Supplement 1, http://links.lww.com/ASAIO/A438 [HM3]; Supplement 2 [HM II], http://links.lww.com/ASAIO/A439, Supplement 3, http://links.lww.com/ASAIO/A440 [HVAD]).

At every step, all TTE and hemodynamic parameters are recorded, and the slope of change of each parameter was calculated using Excel 2011 (Microsoft, Redmond, WA). Continuous variables were expressed as mean ± standard deviation (SD).

Results of Reverse Ramp Testing

Seven LVAD patients (four HM II and three HVAD) underwent reverse ramp testing using the above-described protocol. All patients had non-ischemic cardiomyopathy; average age was 37.1 ± 20.7 years. The mean time interval between the reverse ramp testing and LVAD implantation was 14.0 ± 7.62 months.

Table 1 shows hemodynamic and echocardiographic parameters before LVAD implantation and at the time of presentation for the reverse ramp test. All hemodynamic parameters improved significantly after LVAD implantation except for CVP. Left ventricular end-diastolic diameter decreased from 6.08 ± 1.18 cm to 4.91 ± 0.66 cm (p = 0.06), and left ventricular ejection fraction (LVEF) increased from 19.40% ± 6.84% to 30.67% ± 10.15% (p = 0.06).

Table 1
Table 1:
Hemodynamic and Echocardiographic Parameters 

Changes in echocardiographic parameters during the reverse ramp test are shown in Table 1 and Figure 1. With progressive decreases in LVAD speed, and hence, reloading of the left ventricle, LVEF improved from baseline post-VAD 30.67% ±10.15% to 46.05%±14.19% at the last step (slope 1.9%/stage).

Figure 1
Figure 1:
The trends of hemodynamic and echocardiographic parameters of individual patients for each VAD turn down step are shown. LVEF increased during turn down in all patients and in three patients to above 55%. There was no significant increase in LVEDD. CO increased in two patients during turn down and remained largely unchanged in five patients. There was no change in PA saturation. CO, cardiac output; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; VAD, ventricular assist device.

Left ventricular end-diastolic diameter was unchanged during the reverse ramp test and mild MR developed in one patient (at baseline, MR was graded as trace or not present in all patients). The aortic valve remained open throughout the study in all patients.

The hemodynamic responses to reverse ramp testing are shown in Table 1. During LVAD speed reduction, PCWP increased from 8.86 ± 3.08 mm Hg to 12.50 ± 2.04 mm Hg, mean PAP remained stable (18.29 ± 3.73 mm Hg to 19.00 ± 3.46 mm Hg), and CVP increased minimally from 7.14 ± 2.91 mm Hg to 8.17 ± 3.34 mm Hg. Cardiac output decreased slightly during the test from 5.92 ± 0.55 L/min to 5.44 ± 0.51 L/min.

Plots of CVP versus PCWP for each patient are shown in Figure 2, A and B; the plot representing CVP/PCWP for step 1 is marked in red, and the plot representing the last turn down step is marked in black. These plots are divided into five zones depending on the hemodynamic profiles: normal, left heart failure (LHF), fluid overload, right heart failure (RHF), and hypovolemia (Hypo). At baseline, all patients had PCWPs and CVPs within the normal range consistent with hemodynamic optimization. All patients remained in the normal zone during the reverse ramp study, with two patients moving in the direction of the RHF quadrant (Figure 2B, patient number 5 and 6). Additionally shown in the quadrant plots is the change of LVEF for each patient. Notably, patients with the most significant improvement in LVEF also have the smallest increase in CVP and PCWP (Figure 2A).

Figure 2
Figure 2:
CVP and PCWP plots for individual patients (labeled 1–7) at baseline and every turn down step are shown. Plots are divided into five zones depending on hemodynamic profiles: normal, LHF, fluid overload, RHF, and hypovolemia (Hypo). The plot representing CVP and PCWP for step 1 is marked in red and the plot representing the last turn down step is black. At baseline, all patients were within the normal zone. Change in LVEF is shown for every individual patient plot. A: Patients with favorable hemodynamic response to reverse ramp, considered for LVAD decommissioning. In all cases, LVEF increased to >55%. B: Patients with unfavorable hemodynamic response during turn down. In two patients, there was a trend toward development of RHF/fluid overload. In these patients, LVEF remained depressed during reloading of the LV with speed reduction. CVP, central venous pressure; LHF, left heart failure; LV, left ventricle; LVAD, left ventricular assist device support; LVEF, left ventricular ejection fraction; PCWP, pulmonary capillary wedge pressure; RHF, right heart failure.

As shown in Figure 1, CO increased mildly in two of seven patients and remained stable with a minimal downward trend in five of seven patients. Interestingly, pulmonary artery saturation remained unchanged in all patients with the LVAD speed turned down. Heart rate remained largely unchanged in all patients; only one of seven patients had a drop in Doppler blood pressure.

During ramp testing, three patients increased their ejection fraction to greater than 55% while maintaining normal hemodynamics and left ventricular (LV) size (displayed in Figure 2A and patients marked with an asterix in Figure 1). Two of these patients underwent LVAD decommissioning through occlusion of the outflow graft with a percutaneous device followed by turning off the LVAD. The third patient with a positive response to the ramp study was diagnosed with bladder cancer shortly after the reverse ramp test and died from the malignancy before device decommissioning. All other patients were deemed not suitable for decommissioning due to suboptimal improvement in ejection fraction during the reverse ramp test (Figure 1B and Figure 2 without asterix).

Of the remaining patients, three subsequently underwent cardiac transplantation and one was continued on LVAD support as destination therapy.

Conclusion

The reverse ramp test is a valuable tool for the assessment of myocardial recovery in patients with supported with LVADs. As shown in our series, true assessment of LVEF is not possible while the left ventricle is unloaded by LVAD therapy. Ramping the speed down to minimal LVAD support permits a more accurate assessment of myocardial function and can add decision making regarding device explantation or decommissioning.

Acknowledgment

The authors thank Daniel Rodgers for his invaluable support in data collection.

References

1. Drakos SG, Mehra MR. Clinical myocardial recovery during long-term mechanical support in advanced heart failure: Insights into moving the field forward. J Heart Lung Transplant 2016.35: 413–420
2. Drakos SG, Kfoury AG, Stehlik J, et al. Bridge to recovery: Understanding the disconnect between clinical and biological outcomes. Circulation 2012.126: 230–241
3. Wever-Pinzon O, Drakos SG, McKellar SH, et al. Cardiac recovery during long-term left ventricular assist device support. J Am Coll Cardiol 2016.68: 1540–1553
4. Imamura T, Nguyen A, Kim G, et al. Optimal haemodynamics during left ventricular assist device support are associated with reduced haemocompatibility-related adverse events. Eur J Heart Fail 2019.21: 655–662
Keywords:

left ventricular assist device; myocardial recovery; reverse ramp test

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