Effect Of Left Ventricular Unloading Research Articles

Abstract 17687: Left Ventricular Unloading in Pulmonary Hypertension With Impella 5.5 as a Bridge to Heart Transplantation

A 59 year-old male with a history of triple-vessel coronary artery bypass graft surgery, ischemic cardiomyopathy with an implantable cardioverter defibrillator, pre- and post-capillary pulmonary hypertension, severe mitral regurgitation, paroxysmal atrial fibrillation, diabetes mellitus, hypertension was referred for transplant evaluation in the setting of cardiogenic shock despite inotropic support. His initial right heart catheterization showed RAP 21 mmHg, RVP 91/9 mmHg, PAP 88/31 mmHg with a mean of 50 mmHg, PCWP 22 mmHg, PVR 6.6 Wood units, SVR 857 dynes, and CO 4.85 l/min/CI 2.59 l/min/m 2 by thermodilution. His hospital course was complicated by acute renal failure requiring continuous renal replacement therapy. Inotropic support could not be weaned on multiple attempts, and pulmonary and wedge pressures remained significantly elevated despite a trial of inhaled nitric oxide. The patient underwent Impella 5.5 placement to assess the hemodynamic response of unloading the left ventricle. A repeat right heart catheterization showed a RAP 1 mmHg, RVP 42/1 mmHg, PAP 48/13 mmHg with a mean of 26 mmHg, PVR 2.3 Wood units, SVR 829 dynes, and CO 6.75 l/min/CI 3.74 l/min/m 2 by thermodilution. Measurements were obtained with Impella 5.5 at P-8 level, milrinone 0.2 mcg/kg/min, treprostinil 4 ng/kg/min, epoprostenol 1 mg every 6 hours, and sildenafil 10 mg in morning and afternoon and 15 mg in evening. The patient underwent successful heart and kidney transplantation. Post-transplantation right heart catheterization showed persistent pre-capillary pulmonary hypertension with normal filling pressures and CI. His pulmonary hypertension was managed with sildenafil 40 mg three times daily and ambrisentan 10 mg daily. This case demonstrates favorable hemodynamic effects of left ventricular unloading using Impella support with significant reduction in pulmonary vascular pressure to reach candidacy for heart transplantation.

Effect of Left Ventricular Unloading by Pump Speed Adjustment on Myocardial Flow in Continuous-flow Left Ventricular Assist Device Patients.

Resting myocardial blood flow (MBF) and myocardial flow reserve (MFR) are reduced in heart failure (HF) patients supported by pulsatile left ventricular assist devices (LVADs). The effect of continuous-flow (CF) physiology on these parameters is underexplored in CF-LVAD patients. We investigated the impact of CF-LVADs on resting MBF and MFR under two left ventricular (LV) loading conditions. Nine HeartMate II patients (42 ± 12 years, 100% male) on support for 370 ± 281 days were enrolled. Results were compared with 9 HF patients (58 ± 13 years, 67% male, LV ejection fraction 27 ± 9%) and 10 healthy volunteers (56 ± 10 years, 20% male). CF-LVAD patients underwent transthoracic echocardiography with ramp study. MBF and MFR were measured utilizing positron emission/computed tomography imaging under two LV loading conditions: "high-speed" (HS), promoting aortic valve (AV) closure and LV unloading; "low-speed" (LS), promoting AV opening and LV loading. Global resting MBF was similar in HS, LS, HF, and healthy: 0.8 ± 0.3, 0.7 ± 0.3, 0.7 ± 0.1, 0.9 ± 0.2 ml/min/g, respectively; p = NS. HS global MFR was reduced compared with LS and HF: 1.6 ± 0.6 versus 1.9 ± 0.5, p = 0.004; 1.6 ± 0.6 versus 2.4 ± 0.5, p = 0.01, respectively. HS regional MFR was reduced compared with LS in the left anterior descending (1.7 ± 0.7 vs. 2.0 ± 0.6, p = 0.027) and left circumflex (1.8 ± 0.7 vs. 2.2 ± 0.9, p = 0.008), but not in right coronary artery (1.7 ± 0.7 vs. 1.7 ± 0.6, p = 0.76). Resting MBF is preserved among CF-LVAD patients and is similar to HF and healthy. Promoting LV ventricular unloading with higher speed was associated with lower global and regional left coronary MFR, while right coronary MFR did not change.

Interventricular-Septal Output While Supported on Left Ventricular Assist Device Therapy.

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

Interventricular Septal Output While Supported on LVAD Therapy

Purpose The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. Methods A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data (quantitative and qualitative measures of RV function and LV remodeling) were collected pre-operatively and up to two years following LVAD implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)*heart rate. Results 110 patients (65% male, mean age 57±14yrs) were included. 83 patients (77%) received a HeartWare and 25 patients (23%) received a HeartMate 3. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS’) and TAPSE were observed after implant (P<.0001). However, while LVEF rose slightly on average over the follow-up period, ISO gradually decreased over time (P<.0001), driven by a diminishment of IVSs-IVSd. While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI 1.4-16.5; P=0.012). Conclusion RV function is known to be influenced by unique mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation. The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data (quantitative and qualitative measures of RV function and LV remodeling) were collected pre-operatively and up to two years following LVAD implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)*heart rate. 110 patients (65% male, mean age 57±14yrs) were included. 83 patients (77%) received a HeartWare and 25 patients (23%) received a HeartMate 3. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS’) and TAPSE were observed after implant (P<.0001). However, while LVEF rose slightly on average over the follow-up period, ISO gradually decreased over time (P<.0001), driven by a diminishment of IVSs-IVSd. While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI 1.4-16.5; P=0.012). RV function is known to be influenced by unique mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

Prevention and treatment of pulmonary congestion in patients undergoing venoarterial extracorporeal membrane oxygenation for cardiogenic shock.

Cardiogenic shock is still a major driver of mortality on intensive care units and complicates ∼10% of acute coronary syndromes with contemporary mortality rates up to 50%. In the meantime, percutaneous circulatory support devices, in particular venoarterial extracorporeal membrane oxygenation (VA-ECMO), have emerged as an established salvage intervention for patients in cardiogenic shock. Venoarterial extracorporeal membrane oxygenation provides temporary circulatory support until other treatments are effective and enables recovery or serves as a bridge to ventricular assist devices, heart transplantation, or decision-making. In this critical care perspective, we provide a concise overview of VA-ECMO utilization in cardiogenic shock, considering rationale, critical care management, as well as weaning aspects. We supplement previous literature by focusing on therapeutic issues related to the vicious circle of retrograde aortic VA-ECMO flow, increased left ventricular (LV) afterload, insufficient LV unloading, and severe pulmonary congestion limiting prognosis in a relevant proportion of patients receiving VA-ECMO treatment. We will outline different modifications in percutaneous mechanical circulatory support to meet this challenge. Besides a strategy of running ECMO at lowest possible flow rates, novel therapeutic options including the combination of VA-ECMO with percutaneous microaxial pumps or implementation of a venoarteriovenous-ECMO configuration based on an additional venous cannula supplying towards pulmonary circulation are most promising among LV unloading and venting strategies. The latter may even combine the advantages of venovenous and venoarterial ECMO therapy, providing potent respiratory and circulatory support at the same time. However, whether VA-ECMO can reduce mortality has to be evaluated in the urgently needed, ongoing prospective randomized studies EURO-SHOCK (NCT03813134), ANCHOR (NCT04184635), and ECLS-SHOCK (NCT03637205). These studies will provide the opportunity to investigate indication, mode, and effect of LV unloading in dedicated sub-analyses. In future, the Heart Teams should aim at conducting a dedicated randomized trial comparing VA-ECMO support with vs. without LV unloading strategies in patients with cardiogenic shock.

Abstract 18185: Regression of Severe Left Ventricular Hypertrophy After Transcatheter Valve Replacement for Aortic Stenosis: Impact on Clinical Outcomes in PARTNER Cohort A

Background: Left ventricular (LV) mass regression after aortic valve replacement (AVR) for aortic stenosis (AS) is a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. We examined the effect on clinical outcomes after transcatheter AVR (TAVR) of: 1) amount of LV mass index (LVMi) regression; and 2) persistent severe LV hypertrophy (LVH). Methods: Of 2115 patients with symptomatic AS at high surgical risk receiving TAVR in the PARTNER randomized trial or continued access registry, 462 (55% women) who had severe LVH (LVMi ≥149 g/m 2 men, ≥122 g/m 2 women, by ASE criteria) at baseline (BL) and LVMi measured 6 mo post-TAVR were included in our analysis. The effect of LVMi regression was evaluated by comparing outcomes in patients with greater vs. lesser decrease (dichotomized by median % change) in LVMi between BL and 6 mo, and in those without vs. with persistent severe LVH 6 mo post-TAVR. Cox PH models evaluated rates of all-cause mortality (6-12 mo), rehospitalizations (through 1 yr), and the composite of these two outcomes. Results: LVMi decreased from 173±32 (BL) to 121±25 g/m 2 (6 mo) (p&lt;0.001) in those with greater LVMi regression, and from 164±30 (BL) to 158±34 g/m 2 (6 mo) (p&lt;0.001) in those with lesser LVMi regression. Patients with greater vs. lesser LVMi regression had similar baseline clinical characteristics, a lower rate of rehospitalization (10.5% vs. 19.9%, p=0.006) and lower rate of the composite endpoint of death or rehospitalization (13.2% vs. 21.4%, p=0.02), but a similar rate of death (4.9% vs. 4.8%, p=0.86). Persistent severe LVH at 6 mo post-TAVR was present in 54% (58% of whom were women). Patients without vs. with persistent severe LVH had similar baseline clinical characteristics, a lower rate of rehospitalization (11.9% vs. 18.1%, p=0.053) and lower rate of the composite endpoint of death or rehospitalization (13.3% vs. 20.7%, p=0.03), but a similar rate of death (3.9% vs. 5.7%, p=0.42). Similar results were obtained when including patients with moderate or severe LVH. Conclusions: In high-risk patients with severe AS and severe LVH undergoing TAVR, greater LV mass regression and resolution of initially severe LVH at 6 months are associated with a lower rate of death or repeat hospitalization.

Effects of left ventricular unloading on reperfusion-related AIVR in acute myocardial infarction

Accelerated idioventricular rhythm (AIVR) often occurs in the setting of acute myocardial infarction, specifically after reperfusion. We studied the direct left ventricular (LV) dynamic effects of AIVR compared with sinus rhythm. Furthermore, we observed an interesting finding of LV unloading on the occurrence of AIVR.

Effects of left ventricular unloading by Impella recover LP2.5 on coronary hemodynamics

We studied the effects of LV unloading by the Impella on coronary hemodynamics by simultaneously measuring intracoronary pressure and flow and the derived parameters fractional flow reserve (FFR), coronary flow velocity reserve (CFVR), and coronary microvascular resistance (MR). Patients with compromised left ventricular (LV) function undergoing high-risk percutaneous coronary intervention (PCI) may benefit from LV unloading. Limited information is available on the effects of LV unloading on coronary hemodynamics. Eleven patients (mean LV ejection fraction of 35 +/- 11%) underwent PCI during LV support by the LV unloading device (Impella Recover LP2.5). Intracoronary measurements were performed in a nonstenotic coronary artery after the PCI, before and after adenosine-induced hyperemia at four different support levels (0-2.5 L/min). Aortic and coronary pressure increased with increasing support levels, whereas FFR remained unchanged. Baseline flow velocity remained unchanged, while hyperemic flow velocity and CFVR increased significantly with increasing support levels (61 +/- 24 to 72 +/- 27 cm/sec, P = 0.001 and 1.88 +/- 0.52 to 2.34 +/- 0.63, P < 0.001 respectively). The difference between baseline MR and hyperemic MR significantly increased with increasing support levels (1.28 +/- 1.32 to 1.89 +/- 1.43 mm Hg cm(-1) sec, P = 0.005). Unloading of the LV by the Impella increased aortic and intracoronary pressure, hyperemic flow velocity and CFVR, and decreased MR. The Impella-induced increase in coronary flow, probably results from both an increased perfusion pressure and a decreased LV volume-related intramyocardial resistance.

Effects of acute left ventricular unloading on right ventricular function in normal and chronic right ventricular pressure-overloaded lambs

Objective: Right ventricular pressure overload occurs in several types of (congenital) heart disease, as well as in pulmonary disease. Clinical outcome in some of these patient groups might in part be related to left ventricular loading conditions. The effects of left ventricular unloading on the function of the hypertrophic right ventricle have not been studied. We aimed to study the effects of left ventricular unloading on right ventricular hemodynamics and contractility in an animal model of chronic right ventricular pressure overload. Methods: In lambs the pulmonary artery was chronically banded to increase right ventricular pressure to systemic levels. After 8 weeks, right ventricular contractility and hemodynamic function were assessed in these lambs, as well as in age-matched control animals, by using a combined pressure-conductance catheter in the right ventricle during baseline conditions and during complete bypass of the left ventricle. Results: In both groups acute left ventricular unloading significantly decreased left ventricular pressure to low levels while aortic pressure was maintained. In the right ventricle of the control group, both end-systolic and end-diastolic volumes increased with left ventricular unloading (P <.01) while end-systolic pressure was maintained. Cardiac output was unchanged despite decreased right ventricular contractility. In the banding group acute left ventricular unloading also decreased right ventricular contractility but increased cardiac output. During acute left ventricular unloading, diastolic stiffness was unchanged in the control group, whereas it was significantly decreased in the banding group. Conclusions: Both in normal hearts and in hearts subject to chronic right ventricular pressure overload, acute left ventricular unloading decreases right ventricular contractility. Although no effects on cardiac output are encountered in normal hearts during left ventricular bypass, cardiac output is improved in right ventricular pressure-overloaded hearts, most likely related to improved right ventricular diastolic compliance.J Thorac Cardiovasc Surg 2003;125:481-90