Ventricular Unloading Research Articles

Impact of Concomitant Vasoactive Treatment in Mechanical Left Ventricular Unloading in Profound Cardiogenic Shock

To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on left ventricular (LV) work and end-organ perfusion in a porcine model of profound ischemic cardiogenic shock (CS) supported by Impella CP. CS was induced in 10 pigs by stepwise intracoronary injection of microspheres. After CS was induced and Impella CP support initiated, animals were treated in a blinded crossover design with norepinephrine (0.10 µg/kg/min), epinephrine (0.10 µg/kg/min) or dopamine (10 µg/kg/min) for 30 minutes each. Phenylephrine (10 µg/kg/min) was given at the end of the study for 20 minutes. LV work was estimated using a conductance catheter. Main outcome measure was LV work estimated by pressure volume area (PVA) x heart rate. End-organ perfusion was evaluated by mixed venous oxygen saturation (SVO2) from the pulmonary artery and arterial lactate levels. Multilevel mixed-effects linear regression was used to evaluate treatment effect. All vasoactive drugs induced a significant increase in LV work, borderline for norepinephrine by 92.4 (mmHg*mL)*103/min ⦋95%CI(-1.1, 186), p=0.053)⦌. For all catecholamines, stroke work was significantly increased, but unchanged with phenylephrine, which on the other hand caused a significant increase in potential energy by 483 mmHg*mL ⦋95%CI(195, 772), p=0.001)⦌. SVO2 increased significantly with catecholamines and decreased borderline with phenylephrine by -9 %point ⦋95%CI(-19, 0.49), p=0.063)⦌ which also increased arterial lactate levels by 2.4 mmol/L ⦋95%CI(0.89, 3.92), p=0.002)⦌. There was a trend toward lower arterial lactate levels with norepinephrine by -1.53 mmol/L ⦋95%CI(-3.15, 0.09), p=0.064)⦌ CONCLUSION: Catecholamines increased SVO2 but at the expense of increased LV work, least for norepinephrine and highest for dopamine (figure). Isolated vasoconstriction (phenylephrine) caused an increase in LV work, a decrease in SVO2 and increase in arterial lactate levels.

Validation of Non-Invasive RAMP-Testing for HeartMate 3

RAMP-testing in the postoperative period can be used to optimize LVAD speed for optimal left ventricular unloading, cardiac output, right ventricular function, and LV-RV interactions. We tested the hypotheses that a non-invasive echocardiographic RAMP-test post HM3 implantation improves LV unloading immediately after and 1-3 months after as compared to before the test. We also tested a secondary hypothesis that RPM adjustments during echocardiography-guided RAMP-testing does not worsen RV function immediately after and 1-3 months after. We retrospectively reviewed data from patients followed at our Hospital after HM3 implantation between 2017 and 2019, who had gone through an echocardiographic RAMP-test. A total of 14 out of 19 patients were clinically stable and were enrolled. LVAD speed was increased in 100 RPM increments at 1-minute intervals and echocardiographic images were acquired at every step. Adequate LV unloading was defined as no more than mild mitral regurgitation (MR), and intermittent aortic valve (AV) opening or closed AV, and reduction of LVEDD; and for the follow up measurement, decreased NT-proBNP. Median (IQR) time from implantation to RAMP-test was 27 (16-56) days and median time from RAMP-test to follow up echocardiography was 55 (47-102) days. Median pre-RAMP LVAD speed was 4950 (4875-5225) RPM. Median LVAD speed achieved during RAMP-testing was 5550 (5375;6025) RPM, which was significantly higher than pre-RAMP LVAD speed (p=0.001), and median final LVAD speed was 5200 (5000-5425) RPM, which was also significantly higher than pre-RAMP LVAD speed (p=0.003). RAMP-testing resulted in final LVAD speed increase in 11 (79%) patients and a median net change of 200 (200-300) RPM. Speed adjustments after RAMP-testing resulted in optimized final LVAD speed, manifested as improved LVAD unloading that was achieved in 3 (21%) patients who were not originally optimized. RV function did not worsen significantly during RAMP-testing or at final LVAD speed. Echocardiography-guided RAMP-test allowed LVAD speed adjustment and optimization, and improved LV unloading during RAMP-testing and at final speed with no evidence of worsening of RV function. This study adds to the evidence of echocardiographic RAMP-test as an established, non-invasive and safe technique for speed optimization in HM3 patients.

Intrinsic Myocardial Function and Relationship with Left Ventricular Unloading in Patients Supported on CF-LVAD Therapy

Despite strong interest in left ventricular recovery, no clinical data exist on the relationship between intrinsic myocardial function and reverse remodeling or LVAD unloading. We sought to evaluate this interaction. Patients implanted with continuous flow LVADs between 2015 and 2018 who underwent combined LHC/RHC ramp protocol at a single institution were enrolled. Exclusion criteria were significant valve disease, inability to optimize hemodynamically during ramp study, or inotropic therapy. Hemodynamic data including peak LV dP/dt and tau were obtained. Among a cohort of 62 patients undergoing LHC/RHC study, 25 patients were included (12 with LVEF ≥25%, augLV, and 13 with LVEF <25%, impLV). Important hemodynamic differences between augLV and impLV included aortic pulse width, tau, and peak LV dP/dt. On linear regression, aortic pulse width was associated with each of LV systolic pressure, peak LV dP/dt, and LVEF% (r = 0.58, 0.59, and 0.40 with p < 0.05 for all). Both adjusted tau and LV dP/dt were associated with PCWP values (r = 0.41, p < 0.0001 and r = -0.52, p <0.0001, respectively); however, an inverse relationship between LVAD speed and strength of association with PCWP was noted. Significant correlations between intrinsic myocardial function and reverse remodeling as well as aortic pulsatility were noted. A greater reliance on LVAD for unloading is noted at higher speeds, suggesting excessive LVAD unloading may be detrimental. Future work should focus on defining the optimal level of LVAD support, particularly in relation to LV recovery and functional outcomes.

Non-Pulsatile Flow is Associated with Lower Levels of Circulating CD34+ Cells in LVAD-Supported Patients

The lack of pulsatility may be associated with altered angiogensis in LVAD patients. Since CD34+ cells represent an important regulator of angiogenesis in heart failure, we sought to investigate a potential correlation between flow pulsatility and circulating CD34+ cell levels in this patient population. In a single-center prospective cohort study we measured peripheral CD34+ cell numbers in patients undergoing LVAD support for at least 3 months. Patients with active infection, active hematologic disorders and history of chemotherapy were excluded. Pulsatile flow was defined as aortic valve opening in each cardiac cycle in the setting of optimized left ventricular unloading. Peripheral CD34+ cells were quantified by flow cytometry using the International Society of Hemotherapy and Graft Engineering protocol. Of 12 patients, pulsatile flow was established in 6 patients (Group A) and 6 patients failed to demonstrate flow pulsatility (Group B). The two groups did not differ in age (60±9 years in Group A vs. 59±6 years in Group B, P=0.97), gender (male; 83% vs. 83%, P=1.00), heart failure etiology (ischemic: 50% vs. 52%, P=0.84), serum creatinine (1.10±0.19 mg/dL vs. 0.97±0.17 μmol/L, P=0.35), NT-proBNP (926±587 pg/mL vs. 1562±1190 pg/mL, P=0.35), LDH levels (3.2±0.5 μmol/L vs. 3.4±3.2 μmol/L, P=0.79), length of LVAD support (932±369 days vs. 462±298 days, P=0.10), mean blood pressure (86±9 mmHg vs. 83±4 mmHg, P=0.43) or estimated pump flow (4.8±0.9 L/min vs. 4.3±0.6 L/min, P=0.32). Pulsatility index was higher in Group A than in Group B (5.6±1.2 vs. 3.6±0.6, P=0.006). Despite similar leukocyte counts (6.7±0.9x109/L in Group A vs. 7.3±0.8 x109/L in Group B, P=0.52), hemoglobin (12.6±7.3 g/dL vs. 13.5±1.6 g/dL, P=0.28) and serum iron (16±10 μmol/L vs. 14±5 μmol/L, P=0.66) we found significantly higher peripheral CD34+ cell count in Group A than in Group B (2.4±0.7x106/L vs. 1.6±0.8 x106/L, P=0.03). Overall, CD34+ cell count was inversely related to red cell distribution width (R2=0.-58 , P=0.05). Non-pulsatile flow appears to be associated with lower numbers of peripheral CD34+ cells in LVAD-supported patients. This suggests that hemodynamic changes after prolonged LVAD support may significantly alter angiogenesis and vasculogenesis pathways in chronic heart failure.

Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock

BackgroundConcomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP).ObjectiveTo compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP.MethodsCS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 μg/kg/min), epinephrine (0.10 μg/kg/min), or dopamine (10 μg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 μg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression.ResultsAll catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002).ConclusionCatecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.

Left ventricular unloading during extracorporeal membrane oxygenation - Impella versus atrial septal defect: A simulation study.

Atrial septal defect and Impella have been proposed for left ventricular unloading in venoarterial extracorporeal membrane oxygenation patients. This work aims at evaluating the haemodynamic changes in venoarterial extracorporeal membrane oxygenation patients after Impella implantation or atrial septal defect realization by a simulation study. A lumped parameter model of the cardiovascular system was adapted to this study. Atrial septal defect was modelled as a resistance between the two atria. Venoarterial extracorporeal membrane oxygenation and Impella were modelled starting from their pressure-flow characteristics. The baseline condition of a patient undergoing venoarterial extracorporeal membrane oxygenation was reproduced starting from haemodynamic and echocardiographic data. The effects of different atrial septal defect size, Impella and venoarterial extracorporeal membrane oxygenation support were simulated. Impella caused an increment of mean arterial pressure up to 67%, a decrement in mean pulmonary arterial pressure up to 8%, a decrement in left ventricular end systolic volume up to 11% with a reduction up to 97% of left ventricular cardiac output. Atrial septal defect reduces left atrial pressure (19%), increases right atrial pressure (22%), increases mean arterial pressure (18%), decreases left ventricular end systolic volume (11%), increases right ventricular volume (33%) and decreases left ventricular cardiac output (55%). Impella has a higher capability in left ventricular unloading during venoarterial extracorporeal membrane oxygenation in comparison to atrial septal defect with a lower right ventricular overload.

Early cardiac unloading with ImpellaCP™ in acute myocardial infarction with ventricular septal defect

Despite a relative contraindication, mechanical support with Impella™ left ventricular assist device has already been described for ischaemic ventricular septal defect treatment, either as a bridge to surgery, as intraoperative mechanical haemodynamic support, or to ensure intraprocedural haemodynamic stability during device closure. We describe two cases of ventricular septal defect complicating acute myocardial infarction, where the percutaneous ImpellaCP was implanted early (differently than previously described) with the aim of preventing haemodynamic instability, while deferring surgical repair. We present a report of haemodynamic, echocardiographic, biochemical, and clinical data of two consecutive cases of ImpellaCP use, within a minimally invasive monitoring and therapeutic approach. In two cases of subacute myocardial infarction‐related ventricular septal defect not amenable to percutaneous device closure, the use ImpellaCP was successful: it was followed by effective and rapid right and left ventricular unloading, by major haemodynamic instability prevention and protection from systemic venous congestion, from kidney and splanchnic organ failures. This allowed bridging to appropriately timed surgical repair. These cases suggest a potentially effective, clinically grounded strategy in the early management of ischaemic ventricular septal defect patients, with the aim of deferring surgery beyond the safer 7 days cutoff associated with a lower perioperative mortality.

Validation of non‐invasive ramp testing for HeartMate 3

AimsRamp testing in the postoperative period can be used to optimize left ventricular assist device (LVAD) speed for optimal left ventricular (LV) unloading. We tested the hypothesis that a non‐invasive echocardiographic ramp test post‐HeartMate 3 implantation improves LV unloading immediately after and 1–3 months after as compared with before the test. We also tested a secondary hypothesis that speed adjustments during echocardiography‐guided ramp testing do not worsen right ventricular (RV) function immediately after and 1–3 months after.Methods and resultsWe retrospectively reviewed data from patients who underwent an echocardiographic ramp test. A total of 14 out of 19 patients were clinically stable and were enrolled. Adequate LV unloading was defined as no more than mild mitral regurgitation, and intermittent aortic valve (AV) opening or closed AV, and reduction of left ventricular end‐diastolic diameter (LVEDD); and for the follow‐up measurement, decreased NT‐proBNP. Median (interquartile range) time from implantation to ramp test was 27 (16; 56) days, and median time from ramp test to follow‐up echocardiography was 55 (47; 102) days. Median LVAD speed achieved during ramp testing was 5550 (5375; 6025) revolutions per minute (rpm), and median final LVAD speed was 5200 (5000; 5425) rpm. Ramp testing resulted in final LVAD speed increase in 11 (79%) patients and a median net change of 200 (200; 300) rpm. Speed adjustments after ramp testing resulted in improved LVAD unloading that was achieved in additional 3 (21%) patients who were not originally optimized. RV function did not worsen significantly during ramp testing or at final LVAD speed.ConclusionsThe echocardiographic ramp test allowed LVAD speed adjustment and optimization and improved LV unloading during ramp testing and at final speed with no evidence of worsening of RV function.

Strategies of left ventricular unloading during VA-ECMO support: a network meta-analysis

BackgroundLeft ventricle (LV) unloading during VenoArterial ExtraCorporeal Membrane Oxygenation (VA-ECMO) reduces the risk of LV distention, stagnation and pulmonary congestion resulting from the increased afterload. Lacking direct comparisons between unloading strategies we used network meta-analysis to indirectly compare different unloading approaches. MethodsA literature research was performed to include all studies on VA-ECMO reporting data on mechanical LV unloading. The pre-specified outcome was in-hospital death. ResultsLiterature search identified 389 studies: 16 were included in the analysis (3930 patients). Two strategies of mechanical LV unloading were compared: afterload reduction (IABP) and preload reduction (Impella pump, right upper pulmonary/trans-septal catheters, LV surgical vents). Any LV unloading strategy was associated with mortality reduction with overall OR = 0.54; 95% CI 0.42–0.70; p < .001. Targeting afterload was associated with reduced mortality (OR = 0.61 95% CI 0.46–0.81; p < .001; I2 = 61%), as targeting preload (OR = 0.34 95% CI 0.21–0.55; p < .001; I2 = 0%). Significant between group difference was observed (p = .04): to further explore this we performed a network meta-analysis. Indirect comparisons between afterload and preload reduction were estimated. Any unloading technique was confirmed better than none but preload targeting resulted better than afterload targeting. ConclusionAny unloading strategy in VA-ECMO patients was associated with lower mortality as compared to no-unloading. Preload reduction strategies resulted superior to afterload reduction.

The hemodynamic effect of different left ventricular unloading techniques during veno-arterial extracorporeal life support: a systematic review and meta-analysis.

Pulmonary edema and left ventricular thrombosis may arise during veno-arterial extracorporeal life support due to an increase in cardiac load. This mechanical stress can be reduced through different left ventricular unloading techniques. We set out to quantitatively summarize the hemodynamic effects of available methods in patients treated with veno-arterial extracorporeal life support. Literature was systematically searched for studies reporting left ventricular unloading during veno-arterial extracorporeal life support as reflected by changes in left atrial pressure, pulmonary capillary wedge pressure, diastolic pulmonary artery pressure, or left ventricular end-diastolic pressure. For studies including ⩾10 patients per group, changes in these parameters were pooled using (1) standardized mean differences and (2) ratio of means. Assessment of potential bias was performed for all studies. Eight studies met the inclusion criteria. Reported techniques included use of intra-aortic balloon pump (n = 1), micro-axial blood pump (Impella®, n = 2), left ventricular venting (n = 1), and atrial septostomy (n = 4). Overall, left ventricular unloading was associated with a statistically significant reduction in preload parameters (standardized mean differences = -1.05 (95% confidence interval = -1.24 to -0.86) and ratio of means = 0.60 (0.47 to 0.76)). Effect sizes were strongest for micro-axial blood pump and atrial septostomy (standardized mean differences = -1.11 (-1.55 to -0.68) and -1.22 (-1.47 to -0.96), and ratio of means = 0.58 (0.39 to 0.86) and 0.54 (0.36 to 0.83), respectively). Left ventricular unloading was associated with a significant reduction in left ventricular preload parameters in the setting of veno-arterial extracorporeal life support. This effect may be most pronounced for micro-axial blood pump and atrial septostomy.

Early prediction of transition to durable mechanical circulatory support in patients undergoing peripheral veno-arterial extracorporeal membrane oxygenation for critical cardiogenic shock.

Peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO) has gained increasing value in the management of patients with critical cardiogenic shock (cCS), allowing time for myocardial recovery. Failure of myocardial recovery has life-altering consequences: transition to durable mechanical circulatory support (dMCS), urgent heart transplantation, or withdrawal of support. Clinical factors controlling myocardial recovery under these circumstances remain largely unknown. Using a retrospective cohort, we developed a model for early prediction of transition to dMCS in patients undergoing pVA-ECMO for cCS. To promote myocardial recovery, our clinical management centered around left ventricular pressure unloading, that is, targeting pulmonary capillary wedge pressures (PCWP) ≤18mmHg. We collected demographic data, laboratory findings, inotrope use, and two-dimensional transthoracic echocardiography measurements, all limited to the first 72h of pVA-ECMO (D1-3). Out of 70 patients who were alive after pVA-ECMO, 27 patients underwent implantation of dMCS. There was no significant difference in survival to hospital discharge between patients with or without transition to dMCS. Ejection fractionD1-3 (per 10% increase, OR 0.37 [0.17-0.79]) and amount of inotropic supportD1-3 (OR 4.77 [1.6-14.18]) but neither myocardial wall tension nor PCWP emerged as significant predictors of transition to dMCS. Optimism-corrected c-index (0.90 [0.89-0.90]) revealed an excellent discriminative ability of our model. In summary,our model for early prediction of transition to dMCS in patients with cCS undergoing pVA-ECMO identifies indicators of inotropic state as relevant factors. Absence of markers for myocardial oxygen consumption or left ventricular pressure loading allows us to hypothesize sufficient cardiac unloading in our cohort with PCWP-targeted management.

Pulsatile arterial blood pressure mimicking aortic valve opening during continuous-flow LVAD support: a case report

BackgroundLeft ventricular assist devices (LVAD) have become a common treatment option in advanced heart failure. Lack of aortic valve opening during left ventricular unloading is a common complication and associated with a worse outcome. Maintaining a minimum pulse pressure is an important goal during the early postoperative period after LVAD implantation since it is commonly seen as secure sign of aortic valve opening.Aims/objectiveWe report a case of an LVAD-supported patient with early permanent closure of the aortic valve despite a pulse pressure > 15 mmHg at all times following LVAD implantation. We demonstrate how careful assessment of the invasive arterial blood pressure curve can indicate aortic valve closure irrespective of pulsatile blood flow.MethodA 69-year old male patient with terminal ischemic cardiomyopathy was referred for long-term mechanical circulatory support. Due to mild aortic regurgitation both an aortic bioprosthesis and a continuous-flow left ventricular assist device were implanted. Postoperative echocardiography documented a patent aortic bioprosthesis and an acceptable residual systolic left ventricular contractility. During invasive arterial blood pressure monitoring repetitive transient slight blood pressure decreases followed by slight blood pressure increases coincided with programmed LVAD flushing cycles. Permanent pulsatile flow with a pulse pressure of ≥15 mmHg conveyed systolic opening of the aortic valve. Echocardiography, however, proved early permanent aortic valve closure. In retrospect, transformation of the automated LVAD flushing cycles into visible changes of the arterial blood pressure curve during invasive blood pressure monitoring is indicative of ejection of the complete cardiac output through LVAD itself, and therefore an early clinical sign of aortic valve closure.Discussion/conclusionWe present this interesting didactic case to highlight caveats during the early postoperative period after LVAD implantation. Moreover, this case demonstrates that careful and differentiated observation of the arterial blood pressure waveform provides crucial information in this unique and growing patient population of continuous-flow LVAD support.

Advances in Hemodynamic Analysis in Cardiovascular Diseases Investigation of Energetic Characteristics of Adult and Pediatric Sputnik Left Ventricular Assist Devices during Mock Circulation Support.

The need to simulate the operating conditions of the human body is a key factor in every study and engineering process of a bioengineering device developed for implantation. In the present paper, we describe in detail the interaction between the left ventricle (LV) and our Sputnik left ventricular assist devices (LVADs). This research aims to evaluate the influence of different rotary blood pumps (RBPs) on the LV depending on the degree of heart failure (HF), in order to investigate energetic characteristics of the LV-LVAD interaction and to estimate main parameters of left ventricular unloading. We investigate energetic characteristics of adult Sputnik 1 and Sputnik 2 LVADs connected to a hybrid adult mock circulation (HAMC) and also for the Sputnik pediatric rotary blood pump (PRBP) connected to a pediatric mock circulation (PMC). A major improvement of the LV unloading is observed during all simulations for each particular heart failure state when connected to the LVAD, with sequential pump speed increased within 5000–10000 rpm for adult LVADs and 6000–13000 rpm for PRBP with 200 rpm step. Additionally, it was found that depending on the degree of heart failure, LVADs influence the LV in different ways and a significant support level cannot be achieved without the aortic valve closure. Furthermore, this study expands the information on LV-LVAD interaction, which leads to the optimization of the RBP speed rate control in clinics for adult and pediatric patients suffering from heart failure. Finally, we show that the implementation of control algorithms using the modulation of the RBP speed in order to open the aortic valve and unload the LV more efficiently is necessary and will be content of further research.

Left Ventricular Unloading Increases the Coronary Collateral Flow Index Before Reperfusion and Reduces Infarct Size in a Swine Model of Acute Myocardial Infarction.

BackgroundUnloading the left ventricle and delaying reperfusion reduces infarct size in preclinical models of acute myocardial infarction. We hypothesized that a potential explanation for this effect is that left ventricular (LV) unloading before reperfusion increases collateral blood flow to ischemic myocardium.Methods and ResultsAcute myocardial infarction was induced by balloon occlusion of the left anterior descending artery for 120 minutes in adult swine, followed by reperfusion for 180 minutes. After 90 minutes of occlusion, animals were assigned to 30 minutes of continued occlusion (n=6) or to 30 minutes of support with either an Impella CP (n=4) or venoarterial extracorporeal membrane oxygenation (n=5) with persistent occlusion. The primary end point was measures of microcirculatory blood flow including the collateral flow index (CFI) during left anterior descending artery occlusion as (Pw−RA)/(Pa−RA), where Pa, Pw, and RA are aortic, coronary wedge, and right atrial pressure, respectively. Infarct size was quantified using triphenyltetrazolium chloride. Compared with continued occlusion, Impella, not venoarterial extracorporeal membrane oxygenation, reduced infarct size relative to the area at risk. Before reperfusion, Impella reduced LV stroke work by 25% and increased the CFI by 75%, but venoarterial extracorporeal membrane oxygenation did not. Among all groups, the change in CFI between 90 and 120 minutes correlated inversely with the change in LV stroke work (r 2=0.44, P=0.01) and infarct size (r 2=0.41, P=0.02).ConclusionsWe report for the first time that 30 minutes of LV unloading during coronary occlusion increases the CFI, which correlates inversely with LV stroke work and infarct size. Venoarterial extracorporeal membrane oxygenation failed to increase the CFI and did not reduce infarct size.

Mechanical circulatory support in the context of coronary artery bypass grafting.

With the continuous innovation in mechanical circulatory support as an option for the management of patients in cardiogenic shock from myocardial infarction, it is important to understand the current evidence and recommendations for the use of these devices for patients who require or underwent coronary artery bypass surgery. The use of mechanical circulatory support (MCS) in patients with cardiogenic shock who require or underwent coronary artery bypass surgery has not been well studied. Observational studies have shown that the use of intra-aortic balloon pump or percutaneous ventricular assist devices prior to revascularization lead to better survival. Extracorporeal membrane oxygenation (ECMO) still carries significant risk of mortality and complications; the use of additional MCS devices for left ventricular unloading during ECMO improves outcomes. MCS will continue to play an important role in coronary artery surgery patients. Multidisciplinary Cardiac Shock Team can assist in proper patient selection and device choice, whereas prospective clinical trials are required to provide evidence-based guidance towards the management of these patients.

Benefits of Impella and Peripheral Veno-Arterial Extra Corporeal Life Support Alliance.

Peripheral veno-arterial extra corporeal life support (V-A ECLS) is an effective tool in treating refractory cardiogenic shock (RCS). Despite additional use of intra-aortic balloon pump, insufficient left ventricular unloading is a likely complication. We present herein our experience combining V-A ECLS and Impella to treat symptomatic, critical patients. A retrospective single-center review analyzed patients with V-A ECLS and intra-aortic balloon pump for RCS and subsequently benefiting from Impella implantation, between 2011 and 2015. From 1248 cases, 31 critical patients (2.5%) with a median SOFA score = 12 (7-15) were included. Median age was 53 years, and 74% were male. RCS resulted from myocardial ischemia (52%) and idiopathic dilated myocardiopathy (23%). Forty-seven percentage of patients were treated previously for chronic Heart Failure with reduced Ejection Fraction (HFrEF). Median time between V-A ECLS and Impella implantation was 84 hours (24-186). The Impella median support duration was 8 days (5-10). ECLS and Impella were weaned simultaneously in 26% of patients, 33% were switched to a long-term assistance, and 10% were transplanted. Overall, day-30 survival was 53%. Factors including diabetes, patients aged over 60 years, surgery using extracorporeal circulation, adrenalin infusion, acute myocardial infarction, and chronic HFrEF are associated with day-30 mortality. Chronic HFrEF was an independent risk factor for the day-30 mortality [hazard ratio = 5.28 (1.38-20.21), P = 0.015]. Impella and V-A ECLS combination is a promising association for critical patients presenting symptomatic insufficient LV unloading, for weaning V-A ECLS or testing the right ventricle before a switch to left ventricle assist device support.

Pulmonary artery cannulation to enhance extracorporeal membrane oxygenation management in acute cardiac failure.

Pulmonary artery (PA) cannulation during peripheral venoarterial extracorporeal membrane oxygenation (ECMO) has been shown to be effective either for indirect left ventricular (LV) unloading or to allow right ventricular (RV) bypass with associated gas-exchange support in case of acute RV with respiratory failure. This case series reports the results of such peculiar ECMO configurations with PA cannulation in different clinical conditions. All consecutive patients receiving PA cannulation (direct or percutaneous) from January 2015 to September 2018 in 3 institutions were retrospectively reviewed. Isolated LV unloading or RV support, as well as dynamic support including initial drainage followed by perfusion through the PA cannula, was used as part of the ECMO configuration according to the type of patient and the patient's haemodynamic/functional needs. Fifteen patients (8 men, age range 45-73 years, EuroSCORE log range 14.45-91.60%) affected by acute LV, RV or biventricular failure of various aetiologies, were supported by this ECMO mode. Percutaneous PA cannulation was performed in 10 patients and direct PA cannulation, in 5 cases. Dynamic ECMO management (initially draining and then perfusing through the PA cannula) was carried out in 6 patients. Mean ECMO duration was 9.1 days (range 6-17 days). One patient exhibited pericardial fluid during the implant of a PA cannula (no lesion found when the chest was opened), and weaning from temporary circulatory support was achieved in 14 patients (1 who received a transplant). Three patients (20%) died in-hospital, and 12 patients were successfully discharged without major complications. Effective indirect LV unloading in peripheral venoarterial ECMO as well as isolated RV support can be achieved by PA cannulation. Such an ECMO configuration may allow the counteraction of common venoarterial ECMO shortcomings or allow dynamic/adjustable management of ECMO according to specific ventricular dysfunction and haemodynamic needs. Percutaneous PA cannulation was shown to be safe and feasible without major complications. Additional investigation is needed to confirm the safety and efficacy of such an ECMO configuration and management in a larger patient population.

A Starling-like total work controller for rotary blood pumps: An in vitro evaluation.

Due to improved durability and survival rates, rotary blood pumps (RBPs) are the preferred left ventricular assist device when compared to volume displacement pumps. However, when operated at constant speed, RBPs lack a volume balancing mechanism which may result in left ventricular suction and suboptimal ventricular unloading. Starling-like controllers have previously been developed to balance circulatory volumes; however, they do not consider ventricular workload as a feedback and may have limited sensitivity to adjust RBP workload when ventricular function deteriorates or improves. To address this, we aimed to develop a Starling-like total work controller (SL-TWC) that matched the energy output of a healthy heart by adjusting RBP hydraulic work based on measured left ventricular stroke work and ventricular preload. In a mock circulatory loop, the SL-TWC was evaluated using a HeartWare HVAD in a range of simulated patient conditions. These conditions included changes in systemic hypertension and hypotension, pulmonary hypertension, blood circulatory volume, exercise, and improvement and deterioration of ventricular function by increasing and decreasing ventricular contractility. The SL-TWC was compared to constant speed control where RBP speed was set to restore cardiac output to 5.0 L/min at rest. Left ventricular suction occurred with constant speed control during pulmonary hypertension but was prevented with the SL-TWC. During simulated exercise, the SL-TWC demonstrated reduced LVSW (0.51 J) and greater RBP flow (9.2 L/min) compared to constant speed control (LVSW: 0.74 J and RBP flow: 6.4 L/min). In instances of increased ventricular contractility, the SL-TWC reduced RBP hydraulic work while maintaining cardiac output similar to the rest condition. In comparison, constant speed overworked and increased cardiac output. The SL-TWC balanced circulatory volumes by mimicking the Starling mechanism, while also considering changes in ventricular workload. Compared to constant speed control, the SL-TWC may reduce complications associated with volume imbalances, adapt to changes in ventricular function and improve patient quality of life.

P3476High-resolution respirometry reveals enhanced myocardial mitochondrial ketone oxidation after fasting and ventricular unloading

Abstract Background Impairment of myocardial mitochondrial function is regarded as an established pathomechanism in heart failure. Enhanced oxidation of ketone bodies may potentially exert protective effects on myocardial function. High-resolution respirometry (HRR) resembles a gold-standard methodology to determine myocardial mitochondrial metabolism and oxidative function but has not been validated for ketone substrates yet. Purpose We hypothesized that (1) quantification of ketone body oxidative capacity (OC) in myocardium utilizing ex-vivo HRR is feasible and that (2) ketone-associated OC is elevated after fasting and under conditions of chronic mechanical ventricular unloading. Methods We established new HRR (Oxygraph-2k) protocols, measuring oxygen flux generated by oxidation of the ketone substrates beta-hydroxybutyrate (HBA) and acetoacetate (ACA). Ketone protocols were then applied to twelve C57BL/6 mice' (of which six were fasted for 16h) left ventricular and right liver lobe tissue, as well as to eleven terminal heart failure patients' left ventricular tissue, harvested at heart transplantation. Heart transplant recipients were subdivided into patients with left ventricular assist device prior to transplantation (LVAD group, n=6) or no unloading prior to transplantation (HTX group, n=5). Results In non-fasted rodent hearts, HBA yielded an OC of 25±4 pmol/(s*mg tissue) above basal respiration, when applied as sole substrate (21±11 pmol/(s*mg) in liver). ACA alone did not induce oxygen flux, but ACA+succinate yielded 229% higher oxygen flux than succinate alone in state III (146±32 vs 44±12 pmol/(s*mg); p=0.0003). When titrated after succinate, ACA increased OC by 93±25 pmol/(s*mg) (p=0.0003). In 16h-fasted rodent hearts, HBA-supported OC was 27% higher (41±3 vs 52±9 pmol/(s*mg); p=0.04), while OC with ACA+succinate was unchanged (p=0.60). In rodent liver, no oxygen flux was induced by ACA, reflecting absence of 3-oxoacid CoA-transferase. However, HBA-supported OC was 118% higher in fasted liver (37±13 vs 57±13 pmol/(s*mg); p=0.03). In humans, left ventricular unloading was not associated with altered myocardial OC for fatty acids and glycolytic substrates (standard protocol, p=0.13), but HBA-supported OC was 39% higher in the LVAD group compared to the HTX group (54±12 vs 39±9 pmol/(s*mg), p=0.04). Conclusion Quantification of ketone body OC with HRR is feasible in permeabilized myocardial fibers. Applying this novel method revealed increased HBA-supported myocardial mitochondrial respiration after fasting and chronic left ventricular unloading. These data support a concept of enhanced ketone oxidation following ventricular unloading in myocardial mitochondria. Our findings facilitate new studies on myocardial ketone turnover and the interaction of mitochondrial ketone metabolism with cardiac performance. Acknowledgement/Funding CRC 1116, Research commission of the University Hospital Düsseldorf

P5749Haemodynamical effects o fleft ventricular assistance during high-risk percutaneous coronary interventions with a pneumatic left ventricular assist device

Abstract Background Referral for high-risk percutaneous coronary intervention (PCI) is a progressively growing trend. Percutaneous Mechanical Circulatory Support (MCS), may protect the myocardium and reduce the risk of major adverse events. Clinical data on Left Ventricular (LV) unloading by pneumatically driven Percutaneous Left Ventricular Assist Devices (pVAD's) is currently scarce. Purpose Describe the unloading pattern produced by a pneumatically driven pulsatile pVAD on LV haemodynamics through real-time Pressure-volume (PV) analysis with a conductance catheter positioned in the left ventricle. Methods 19 patients undergoing high-risk PCI treated with MCS were monitored with PV loops and pulmonary artery catheterization throughout the intervention. Results When activated on 1:1 assist ratio, the mean output produced by the pVAD was 1.36±0.13L/min. Compared to pre-implantation, 1:1 support produced a significant reduction in End-systolic Wall Stress (ΔWSes: −11.95%, p&lt;0.01) and PV area (ΔPVA: −16.67%, p&lt;0.01). Contractility did not significantly change (ΔV100: +29.48%, p=0.073; End-systolic Elastance, ΔEes: 1.24%, p=0.86). Effective Arterial Elastance (Ea), representing afterload, decreased (ΔEa: −12.05%, p&lt;0.05). Total Arterial Compliance (ΔTAC: +31.59, p&lt;0.01) increased and Ventricular-arterial Coupling (ΔEa/Ees: −9.79%, p=0.06) non-significantly improved. Mean arterial pressure non-significantly decreased (ΔMAP: −6.66%, p=0.06) and global Cardiac Output remained stable (ΔCO: −0.06%, p=0.37). When the pVAD was removed after the PCI these changes were reversed (Figure 1). Image 1 Conclusion High-risk PCI with pneumatic MCS may result in LV unloading and reduced myocardial oxygen consumption. Further insights will be released in the PULSE trial (Clinicaltrials.gov NCT03200990).