Conductance Catheter Assessment of Left Ventricular Pressure and Volume
Changes in LV pressure and volume were assessed using a 5 Fr conductance catheter system (Sigma-M; CD Leycom, The Netherlands) deployed via the left carotid into the LV (Figure 1C). Ventricular pressure and volume were measured using a solid-state pressure transducer and dual-field excitation mode, respectively, as previously described.5–7 Measurements were acquired at baseline, after introduction of the CP device at P0 followed by P8, after removal of the CP device, and after activation of the TH device at submaximal flow and maximal flow. In brief, the method measures time-varying electrical conductance across five to seven ventricular blood segments delineated by selected catheter electrodes. Correct positioning of the conductance catheter along the long-axis of the LV was confirmed by fluoroscopy. Time-varying segmental conductance has been shown to reflect segmental LV volumes in prior preclinical and clinical studies.5–7 Parallel conductance was assessed by injecting 20 ml of hypertonic (6%) saline into the right internal jugular vein. Absolute LV volumes were measured by subtracting parallel conductance from total conductance volumes. Native LV stroke volume is calculated as the difference in conductance volumes at dP/dt max and dP/dt min. Left ventricular stroke work was calculated as the product of peak LV peak systolic pressure and native stroke volume. Preload recruitable stroke work (PRSW) was calculated as the ratio LVSW and LV end-diastolic volume (LVEDV) using the single-beat method as previously reported.8
Results are presented as mean ± standard deviation (SD). All data within groups were analyzed by nonparametric two-way repeated measures ANOVA on ranks followed by a Holm–Sidak comparison if warranted. All statistical analyses were performed with SigmaStat version 3.1 (Systat Software, Inc. San Jose, CA). An α level of p < 0.05 was considered to indicate a significant effect or between-group difference.
Hemodynamics of Matched Flows via the Impella CP and TandemHeart Devices
Left anterior descending occlusion significantly reduced LVSW, PRSW, contractility (dP/dt max), and LV end-systolic pressure (LVESP) consistent with acute left heart injury (Table 1; Figure 3). Compared with values before LAD occlusion (baseline), maximal activation of the CP reduced LVSW, PRSW, contractility (dP/dt max), and LVESP (Table 1; Figure 3). Compared with postinfarct values, maximal activation of the CP reduced LVSW and LVESP (Table 1; Figures 3 and 4). Compared with baseline values, activation of the TH at matched flows to the CP (3.1 LPM), reduced native stroke volume, LVSW, PRSW, dP/dt max, and LVEDV (Table 1; Figure 3). Compared with postinfarct values, the TH at 3.1 LPM reduced native LV stroke volume, LVSW, and LV end-diastolic pressure (LVEDP; Table 1; Figures 3 and 4). Compared with the CP, the TH at 3.1 LPM of flow had a higher LVESP, otherwise all other variables were similar between the two pumps at matched flows.
Hemodynamics of Maximal TandemHeart Flow versus Maximal CP Flow
To explore whether increased flow through the LA cannula further alters LV hemodynamics, we increased the TH to a maximal RPM setting of 7,500, which generated 4.4 LPM of flow. Compared with baseline values, the TH at 4.4 LPM decreased native stroke volume, LVSW, PRSW, dP/dt max, LVEDV, LVESP, and LVEDP (Table 1; Figure 3). Compared with postinfarct values, the TH reduced native stroke volume, LVSW, PRSW, and LVEDV (Table 1; Figures 3 and 4). Compared with the CP, the TH at 4.4 LPM had a greater reduction in native stroke volume, LVSW, and PRSW, but had a higher LVESP (Table 1; Figure 3). Compared with the TH at 3.1 LPM of flow, a trend towards lower LVSW and PRSW was observed (p = 0.09 and p = 0.06, respectively) with maximal TH activation.
This is the first report to directly compare the effects of LA cannulation using the TH device and retrograde, trans-aortic LV using the CP on LV hemodynamics. Our central finding is that at matched flow rates LA or LV positioning of the inflow cannula provide similar degrees of LV unloading in a bovine model of acute left heart injury. Specifically we report that: 1) at matched flows, both trans-aortic LV cannulation using the CP and LA cannulation using the TH reduce LVSW, 2) the TH reduced LV stroke volume, whereas the CP did not, 3) the CP reduced LVESP, whereas the TH did not, and 4) at maximum flow (4.4 LPM), the TH further reduced LV stroke volume and LVSW compared with the CP. These findings suggest that although the magnitude of LVSW reduction is similar at matched flows, LA or LV positioning of the inflow cannula generate distinct profiles of LV unloading. These data further suggest that use of the TH with a 17 Fr arterial outflow cannula generates higher flow and a greater magnitude of LV unloading than the CP. These findings have potentially important implications for clinical decision-making and for the design of future percutaneously delivered circulatory support devices.
Surgically implanted left ventricular assist devices (LVADs) have evolved from large, bulky pulsatile systems to smaller, compact, fully implantable continuous flow pumps that generate minimally pulsatile blood flow when functioning optimally. Several prior studies have examined the hemodynamic impact of LA versus apical LV cannulation using pulsatile pumps and continuous flow pumps.9–13 In parallel to the evolution of surgical LVADs, percutaneously delivered MCS systems have also grown from counter-pulsation balloon systems to centrifugally driven circuits, or catheter-mounted axial-flow pumps. The Impella family of trans-aortic, axial-flow pumps includes two percutaneously delivered sizes, which achieve an estimated 2.5 and 3.5 LPM of flow.14 A third Impella pump can achieve an estimated 5.0 LPM of flow, however requires surgical vascular access through a conduit graft. Unlike LV apical cannulation, trans-aortic delivery may initially increase LVSW until the pump is activated by inducing transient aortic regurgitation.15 Remmelink et al.16 reported decreased LVEDP, but no change in LVSW, LV volumes, or cardiac output with maximal activation of the Impella 2.5 LP device in 11 patients presenting for high-risk coronary intervention. In 2007, Sauren et al.17 reported a 50% reduction in LVSW with a larger Impella prototype device that generated 3.8 LPM of flow in a preclinical model of acute LV injury.
The TH device requires trans-septal puncture for delivery of a 21 Fr inflow cannula into the LA and can provide 3.0 to 5.0 LPM of flow via percutaneous application depending on the size of the outflow (arterial) cannula, which range between 15 Fr and 19 Fr in clinical application.3 By draining the LA, the primary effect of the TH device is reduced LV preload. Prior reports have shown that positioning of the outflow cannula impacts the magnitude of LV unloading. Specifically, LA-to-ascending aortic bypass will increase LVSW, whereas LA-to-descending aortic bypass greatly reduces LVSW. Theoretically by transferring blood volume from the left atrium to the arterial system, the TH device pressurizes the aorta.4 In the ascending aortic position, this increase in afterload limits the magnitude of LV unloading.18 In the descending aorta, the increase in afterload is mitigated by retrograde perfusion of run-off vessels including the mesenteric, renal, and great vessels of the aortic arch, thereby allowing for a reported 66% reduction in LVSW.19
No studies have previously neither examined the hemodynamic effect of the CP device nor directly explored the effect of the CP versus the TH device. To compare these two percutaneously delivered systems in the same animal, an open-chest, surgical approach was required. Maximal activation of the CP generated 3.1 LPM of flow, which corresponded to a 32% and decrease in LVSW compared with postinfarct values. To compare the effect of the TH to maximal CP activation, the TH was set at 5,500 RPMs which generated 3.1 LPM of flow and a corresponding 39% reduction in LVSW compared with postinfarct values. Although both systems reduced LVSW to similar degrees, the primary effect of the CP was a reduction in LVESP, whereas the primary effect of the TH was a reduction in LVEDV. Notably, the TH was associated with a higher LVESP than the CP, which may be related to increased afterload. Maximal activation of the TH at 7,500 RPMs further reduced LVSW and LVEDV with a persistent increase in LVESP compared with the CP. These data indicate that both retrograde, trans-aortic cannulation of the LV (CP device) and LA–FA bypass (TH device) effectively reduce LVSW by reduced LVESP or LVEDV, respectively.
Given the rising use of acute MCS, these data support the use of both the CP and TH to unload the LV. The CP requires a single-arterial access and can be rapidly deployed in emergent situations by most interventional cardiologists. However, the CP cannot be used in the setting of severe aortic regurgitation or LV thrombus. In contrast, the TH requires large bore arterial and venous access and technical expertise in trans-septal puncture, however, can be used in the setting of severe aortic regurgitation and LV thrombus. The TH cannot be used in the setting of LA thrombus. Our findings suggest that although both devices reduce LVSW, maximal activation of the TH provides a superior reduction in LVSW compared with the CP. The cost of this superior degree of unloading, however, must be weighed against the technical challenges and time required to implant the TH. Further studies are required to delineate which patient populations (i.e., AMI, decompensated heart failure, cardiogenic shock, or high risk intervention) may derive benefit from one approach versus the other.
There exist several limitations with this study. First, an open-chested animal model was used thereby limiting our ability to study the hemodynamics of these devices with an intact pericardium. Second, the number of animals studied was small; however, by implanting both devices in the same animal, we were able to generate rarely available comparative data in the same animal. Given the small n numbers, the statistical analysis should be interpreted with caution. Third, we did not study device effects in a chronic model of LV failure with a diseased microcirculation. Future studies involving larger animal numbers and longer duration of LV support are required.
In conclusion, these data show that devices designed to remove blood from the LA or LV can effectively reduce LVSW by primarily reducing LV volume or pressure, respectively. The technical aspects of device deployment including the use of trans-septal puncture, larger bore cannulas, and the need for surgical vascular access to place larger pumps will continue to guide clinical decision making. Findings from this analysis may inform the design of future devices and the development of prospective clinical studies to evaluate the role of acute circulatory support devices.
1. Werdan K, Gielen S, Ebelt H, Hochman JS. Mechanical circulatory support in cardiogenic shock. Eur Heart J. 2014;35:156–167
2. Sayer GT, Baker JN, Parks KA. Heart rescue: the role of mechanical circulatory support in the management of severe refractory cardiogenic shock. Curr Opin Crit Care. 2012;18:409–416
3. Kar B, Gregoric ID, Basra SS, Idelchik GM, Loyalka P. The percutaneous ventricular assist device in severe refractory cardiogenic shock. J Am Coll Cardiol. 2011;57:688–696
4. Burkhoff D, Naidu SS. The science behind percutaneous hemodynamic support: A review and comparison of support strategies. Catheter Cardiovasc Interv. 2012;80:816–829
5. Baan J, van der Velde ET, de Bruin HG, et al. Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation. 1984;70:812–823
6. Kass DA, Yamazaki T, Burkhoff D, Maughan WL, Sagawa K. Determination of left ventricular end-systolic pressure-volume relationships by the conductance (volume) catheter technique. Circulation. 1986;73:586–595
7. Schreuder JJ, van der Veen FH, van der Velde ET, et al. Left ventricular pressure-volume relationships before and after cardiomyoplasty in patients with heart failure. Circulation. 1997;96:2978–2986
8. Ferrazzi P, Senni M, Iascone MR, et al. Implantation of an elastic ring at equator of the left ventricle influences cardiac mechanics in experimental acute ventricular dysfunction. J Am Coll Cardiol. 2007;50:1791–1798
9. Kirklin JK, Naftel DC, Pagani FD, et al. Sixth INTERMACS annual report: A 10,000-patient database. J Heart Lung Transplant. 2014;33:555–564
10. Feldman D, Pamboukian SV, Teuteberg JJ, et al.International Society for Heart and Lung Transplantation. The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary. J Heart Lung Transplant. 2013;32:157–187
11. Lohmann DP, Swartz MT, Pennington DG, McBride LR, Reedy JE, Miller L. Left ventricular versus left atrial cannulation for the Thoratec ventricular assist device. ASAIO Trans. 1990;36:M545–M548
12. Laks H, Hahn JW, Blair O, et al. Cardiac assistance and infarct size: Left atrial-to-aortic vs left ventricular-to-aortic bypass. Surg Forum. 1976;27:226–228
13. Tevaearai HT, Mueller XM, Jegger D, Horisberger J, Von Segesser L. Atrial, ventricular, or both cannulation sites to optimize left ventricular assistance? ASAIO J. 2001;47:261–265
14. Chan W, Seidelin PH. Trans-aortic percutaneous heart valve deployment of Impella CP™ to assist in high-risk percutaneous coronary intervention. Heart Lung Circ. 2014;23:e142–e144
15. Valgimigli M, Steendijk P, Serruys PW, et al. Use of Impella Recover® LP 2.5 left ventricular assist device during high-risk percutaneous coronary interventions; clinical, haemodynamic and biochemical findings. EuroIntervention. 2006;2:91–100
16. Remmelink M, Sjauw KD, Henriques JP, et al. Effects of mechanical left ventricular unloading by Impella on left ventricular dynamics in high-risk and primary percutaneous coronary intervention patients. Catheter Cardiovasc Interv. 2010;75:187–194
17. Sauren LD, Accord RE, Hamzeh K, et al. Combined Impella and intra-aortic balloon pump support to improve both ventricular unloading and coronary blood flow for myocardial recovery: An experimental study. Artif Organs. 2007;31:839–842
18. Kono S, Nishimura K, Nishina T, et al. Autosynchronized systolic unloading during left ventricular assist with a centrifugal pump. J Thorac Cardiovasc Surg. 2003;125:353–360
19. Goldstein AH, Pacella JJ, Clark RE. Predictable reduction in left ventricular stroke work and oxygen utilization with an implantable centrifugal pump. Ann Thorac Surg. 1994;58:1018–1024
Keywords:Copyright © 2015 by the American Society for Artificial Internal Organs
circulatory support; heart failure; hemodynamics