Echocardiographic Markers of Left Ventricular Unloading

Echocardiographic Markers of Left Ventricular Unloading

Using a Centrifugal-Flow Rotary Pump

SUPPLEMENTARY MATERIAL

RAMP TEST PROTOCOL (COMPLETE METHODOLOGY)

All subjects underwent a complete M-mode, two-dimensional, Doppler and tissue Doppler echocardiographic examination using a Sonos 7500 or iE33 system (Philips Medical Systems, Andover, MA). The ramp study was cancelled if the baseline echocardiographic imaging revealed an aortic root, coronary cusp, or intraventricular thrombus. Appropriate anticoagulation level was confirmed (international normalized ratio > 1.8 or PTT > 60s) prior to performing all ramp tests. All patients also had a baseline LDH level prior to ramp testing and any patient with an up-trending value or other evidence for suspected thrombus was excluded from analysis in this study.

Once all baseline data had been recorded and the patient was deemed an appropriate candidate for speed ramp optimization, the speed was decreased every minute by 200 RPM until the speed was settled at 2200 – 2400 RPM (initial lower limit set at the discretion of the supervising clinician), at which point the devicewas allowed to equilibrate at the new speed for two minutes. The increment of 200 RPM was selected because previously described ramp protocols involving the HeartMate II LVAD used speed change increments of 400 RPM and an increment of 200 RPM for the HVAD in our experience has been a simple, well-tolerated, and reasonably proportional increment.1The general approach by the clinician supervising the ramp study (each overseen by A.J.S to maintain protocol consistency) was to decrease the speed to a lower limit that allowed for the aortic valve to open on every beat. After two minutes, the following echocardiographic measurements were obtained: leftventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD),frequency of aortic valve opening, degree of aortic regurgitation, degree of mitral regurgitation, estimated pulmonary arterial systolic pressure, estimated mitral inflow E wave velocity, and the position of the interventricular septum. In addition, Doppler measured mean arterial pressure, pump power (Watts), and pump estimated flow (L/min) were recorded for each speed.

More specifically, the following echocardiographic parameters were recorded utilizing a single, trained sonographer experienced with imaging the HVAD patients(blinded to the study hypothesis) also supervised by a clinician (A.J.S. for all ramp studies) to ensure consistency in the protocol methods. The supervising clinician, however, did not influence or retrospectively amend the sonographer measurements so as to avoid introducing bias. In the parasternal long-axis view (PLAX) the LVEDD was measured in accordance with standarddimension assessment guidelines,2with attention to ensure the frameused to measure LVEDD was timed near the onset of the QRS to mark the end of diastole. Similarly, LVESDwas measured with attention to ensure the frame used was timed immediately prior to mitral valve opening. Also in the PLAX view, the degree of aortic regurgitation and mitral regurgitation was recorded (grades 1-6). Grading was performed in a method analogous tothose previously described1using visual estimation of color Doppler as follows: grade 1 = trace, grade 2 = mild, grade 3 = mild-moderate, grade 4 = moderate, grade 5 = moderate-severe, grade 6 = severe. Using M-mode to sample at least 5 beats in the PLAX or parasternal short-axis(PSAX) view, the frequency of aortic valve (AV) opening was recorded as the proportion of opening beats (indiscriminate of AV opening time). In the apical four-chamber view the tricuspid regurgitation velocity was sampled in order to estimate the pulmonary arterial systolic pressure (mmHg) via the modified Bernoulli equation. The tricuspid annular plane systolic excursion (TAPSE) was also measured in this view. Finally, when not limited by waterfall artifact from the HVAD, every attempt was made to measure the mitral inflow E velocity (cm/s)in the apical four-chamber view as a potential surrogate of left ventricular filling pressure.3

Following the measurement of the described parameters the pump speed was increased by an increment of 200 RPM and all measurements were repeated after two minutes of equilibration. The ramp protocol was continued until the speed at which point any of the following occurred: 1) the aortic valve remained closed on every beat and the speed was 200 RPM higher than the speed at which the aortic valve was first noted to be persistently closed, 2) there was evidence of impending suck down (increased ectopy on telemetry associated with inlet cannula abutting the interventricular septum) or 3) sudden change in symptoms. These three criteria were based on the principle of avoiding speeds at which no benefit would be expected and concern for harm was justified. Finally, the HVAD was returned to its baseline speed or changed to a new speed at the discretion of the clinician—targeting a speed allowing for intermittent aortic valve opening with a midline interventricular septum, while avoiding increased mitral regurgitation or aortic regurgitation.

SUPPLEMENTARY DISCUSSION: MECHANISM

The underlying mechanism to explain why LVEDD slope appears to be nearly zero for the HVAD centrifugal-flow pump requires further investigation. However, it has been established that the centrifugal-flow pump has a flatter slope forpressure-flow curve(also known as “head pressure”-flow or “H-Q”flow curves) when compared to the axial-flow H-Q curves which typically have a steeper and more linear slope.4For any given increase in pressure gradient (ventricular-aortic differential pressure) across the HVAD centrifugal-flow pump (the so-called “head pressure”, or “H”), there is a more dramatic decrease in flow (“Q”) through the pump in contrast to theaxial-flow pump. This is particularly exaggerated during diastole at which point the pressure gradient is at its highest point and the relative flow through the pump is most diminished. The “H-Q”curvefor each type of rotary pump is an intrinsic property unique to that pump that is defined during preclinical testing. Theoretically any excessive unloading of the ventricle achieved by a higher speed coincident with higher afterload may consequently increase the “H” across the pump, leading to a momentary decrease in “Q” through the pump, especially in diastole when the “H” gradient is highest. Once the ventricle is allowed to fill again and preload returns to its steady state, the “H” across the HVAD pump would decrease and “Q” through the pump would increase.

In effect, the “H-Q”profile intrinsic to the HVAD mayresist significant acute changes in left ventricular end-diastolic geometry at varying pump speed. These hypotheses require further investigation. Finally, acute observations involving LVEDD during a ramp study should not be compared with reductions in LVEDD observed chronically in recent studies which may partially reflect the distinctly different process of LV reverse remodeling.5-9

SUPPLEMENTARY DISCUSSION: LIMITATIONS

The following limitations should be considered when interpreting the results of our study. We conducted a retrospective single center analysis of echocardiographic data measured by sonographers certified in standardized image acquisition using a standardized physician supervised protocol.Furthermore, a sample size of 15 subjects is modest; thus, it is possible that a larger sample size would have demonstrated a statistically significant decrease in LVEDD. However, given the very small standard deviation in LVEDD slope (SD ± 0.0003) it is unlikely a larger sample size would have altered the potentialrelevance of these findings.Additionally, while most subjects underwent ramp study during index hospitalization prior to discharge, a minority of the studies were performed in the outpatient setting. However, LVEDD changed minimally in virtually all patients so the timing of study seemingly had no apparent impact on the results.

Our ramp protocol differs from those previously published focusing on axial flow1 and is designed based on our prior clinical experience and the ease of use for our echocardiography laboratory. Validating the correct ramp protocols for varying LVAD devices is an appropriate future consideration. While the methods for recording LVEDD were in accordance with current guidelines, measurement bias may have been introduced since sonographers at our center have beenpreviously trained to anticipate a decrease in LVEDD as the pump speed is increased. However, any such introduced bias would be expected to lead to a greater negative LVEDD slope and a greater overall decrease in the LVEDD measurements with serially increasing ramp speed. The fact that we found no significant change in LVEDD despite such a potential for bias seemingly reinforces the validity of this observation.

Our results should not be interpreted to suggest that ramp studies, used for optimization of HVAD speed, are either effective or ineffective in reducing future complications of non-pulsatile flow. Adoption of ramp protocols into routine practice has not become standardized for all centers. While such strategies require further study, this analysis was not designed to validate ramp protocol methods or to evaluate outcomes related to the ramp study. This retrospective study was descriptive in nature, with the aim to better understand dynamic echocardiographic markers of ventricular unloading as they pertain to the centrifugal-flow rotary pump. Using this observational data an appropriate prospective study may be better designed to validate ramp protocols involving these patients.

Another potential limitation requiring consideration when interpreting these results is that the HVAD ramp protocol has not been tested or validated in our center or in any other center and there is currently no agreed upon protocol recommended by consensus statements. Our ability to develop and validate our ramp protocol was limited by not knowing a prioriwhich parameters could be reliably measured (since this device is more novel than those used in previously published ramp studies) and also by the lack of data describing echocardiographic techniques unique to the HVAD. It is worth noting that artifact limitations unique to the HVAD made it particularly challenging to reliably measure supplementary echocardiographic markers of left ventricular unloading (discussed previously). Subsequent prospective cohort studies or even randomized controlled trials will be necessary for ramp protocol validation.

Finally, grading of aortic and mitral regurgitation in the setting of a left ventricular rotary pump is poorly defined and current metrics rely on color Doppler visual estimation which has certain known and possibly unknown limitations. However, until a newer grading system is developed and validated, we based our grading system consistent with that of previous derivation cohort studies.1

REFERENCES

1.Uriel N, Morrison KA, Garan AR, Kato TS, Yuzefpolskaya M, Latif F, Restaino SW, Mancini DM, Flannery M, Takayama H, John R, Colombo PC, Naka Y, Jorde UP. Development of a novel echocardiography ramp test for speed optimization and diagnosis of device thrombosis in continuous-flow left ventricular assist devices: The columbia ramp study. Journal of the American College of Cardiology. 2012;60:1764-1775.

2.Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, St John Sutton M, Stewart WJ. Recommendations for chamber quantification: A report from the american society of echocardiography’s guidelines and standards committee and the chamber quantification writing group, developed in conjunction with the european association of echocardiography, a branch of the european society of cardiology. Journal of the American Society of Echocardiography. 2005;18:1440-1463.

3.Estep JD, Stainback RF, Little SH, Torre G, Zoghbi WA. The role of echocardiography and other imaging modalities in patients with left ventricular assist devices. JACC: Cardiovascular Imaging. 2010;3:1049-1064.

4.Moazami N, Fukamachi K, Kobayashi M, Smedira NG, Hoercher KJ, Massiello A, Lee S, Horvath DJ, Starling RC. Axial and centrifugal continuous-flow rotary pumps: A translation from pump mechanics to clinical practice. The Journal of Heart and Lung Transplantation. 2013;32:1-11.

5.Jacobs S, Geens J, Rega F, Burkhoff D, Meyns B. Continuous-flow left ventricular assist devices induce left ventricular reverse remodeling. The Journal of Heart and Lung Transplantation. 2013;32:466-468.

6.Morgan JA, Brewer RJ, Nemeh HW, Murthy R, Williams CT, Lanfear DE, Tita C, Paone G. Left ventricular reverse remodeling with a continuous flow left ventricular assist device measured by left ventricular end-diastolic dimensions and severity of mitral regurgitation. Asaio J. 2012;58:574-577.

7.Klotz S, Deng MC, Stypmann J, Roetker J, Wilhelm MJ, Hammel D, Scheld HH, Schmid C. Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support. Ann Thorac Surg. 2004;77:143-149.

8.Drakos SG, Wever-Pinzon O, Selzman CH, Gilbert EM, Alharethi R, Reid BB, Saidi A, Diakos NA, Stoker S, Davis ES, Movsesian M, Li DY, Stehlik J, Kfoury AG. Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: Insights into cardiac recovery. Journal of the American College of Cardiology. 2013;61:1985-1994.

9.Hosseini MT, Popov AF, Simon AR, Amrani M, Bahrami T. Comparison of left ventricular geometry after heartmate ii and heartware left ventricular assist device implantation. J Cardiothorac Surg. 2013;8:1749-8090.

SUPPLEMENTARY FIGURE LEGENDS

Figure 1:

Title: Initial LVEDD vs. final LVEDD for each ramp series

Caption: For each ramp study series, the LVEDD associated with the initial lowest speed in the study is compared to the LVEDD associated with the final highest speed in the study. This figure represents visually what is described in Table 2, demonstrating no significant change in LVEDD (p= 0.28) from the lowest speed (LVEDD 6.1 ± 0.8 cm) to the highest speed (LVEDD 5.8 ± 0.7 cm) during the ramp study.

Figure 2:

Title: Parasternal short-axis views at low (2200 RPM) and high (3000 RPM) speed

Caption: The interventricular septum was best visualized in the mid-papillary parasternal short-axis view during each ramp study. Represented here is an example of interventricular septal flattening that was occasionally seen at high speeds (3000-3200 RPM) after the aortic valve was noted to be persistently closed. For typical operational speeds (2500-2900 RPM) the septum position and morphology did not appear to change significantly.

SUPPLEMENTARY TABLES

Table 1. Baseline Characteristics

Characteristic / Parameter / All patients
(N=15)
Age (years) / 54 ± 18
Male (n, %) / 15 (100)
Etiology of CM, ischemic (n, %) / 8 (54)
Concomitant surgical procedures (n, %)
Mitral valve repair / replacement / 1 (7)
Aortic valve repair / replacement / 0 (0)
Tricuspid valve repair / 4 (27)
Parameters
Heart rate (bpm) / 86 ± 19
Doppler mean arterial pressure (mmHg) / 77 ± 10
Speed (RPM) / 2648 ± 302
Power (Watts) / 4.0 ± 1.3
Estimated pump flow (L/min) / 5.1 ± 1.0
LVESD (cm) / 5.4 ± 0.9
LVEDD (cm) / 6.0 ± 0.7
Mitral regurgitation grade* / 2.2 ± 1.2
Aortic regurgitation grade* / 1.2 ± 0.5

CM = cardiomyopathy, bpm = beats per minute,RPM = revolutions per minute,

LVESD = left ventricular end-systolic dimension

LVEDD = left ventricular end-diastolic dimension

*see numerical grading in methods section to correlate regurgitation degree

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SUPPLEMENTARY FIGURES

Figure 1. Initial LVEDD vs. final LVEDD for each ramp series.

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Figure 2. Parasternal short-axis views at low (2200 RPM) and high (3000 RPM) speed.

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