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At fixed speed, the spontaneous increase in pump flow accompanying exercise in patients with continuous flow left ventricular assist devices (cfLVADs) is slight in comparison to normal physiologic response, limiting exercise capacity. We systematically exercised 14 patients implanted with an isolated HeartWare HVAD undergoing routine right heart catheterization at baseline and at maximal safe pump speed. In addition to hemodynamics, mixed venous oxygen saturation (SvO2), echocardiography and noninvasive mean arterial pressure, and heart rate were measured. Significantly greater pump flows were achieved with maximum pump speed compared with baseline speed at rest (mean ± standard deviation [SD]: 5.0 ± 0.7 vs. 4.6 ± 0.8 L/min) and peak exercise (6.7 ± 1.0 vs. 5.9 ± 0.9 L/min, p = 0.001). Pulmonary capillary wedge pressure was significantly reduced with maximum pump speed compared to baseline pump speed at rest (10 ± 4 vs. 15 ± 5 mmHg, p < 0.001) and peak exercise (27 ± 8 vs. 30 ± 8 mmHg, p = 0.002). Mixed venous oxygen saturation decreased with exercise (p < 0.001) but was unaffected by changes in pump speed. In summary, although higher pump speeds synergistically augment the increase in pump flow associated with exercise and blunt the exercise-induced rise in left heart filling pressures, elevated filling pressures and markedly diminished SvO2 persist at maximal safe pump speed, suggesting that physiologic flow increases are not met by isolated cfLVADs in the supported failing heart.

We evaluated mean, peak, and instantaneous pressure gradients across the outflow conduit in a pulsatile mock circulation loop which incorporated Heartware HVADs for left ventricular (LV) and right ventricular (RV) support. Steady-state 50 Hz measurements of left ventricular assist device (LVAD) flow (Q) and pressures within the proximal and distal outflow conduit were obtained at varying pump speed, LV contractility, hematocrit (HCT), heart rate (HR), and conduit diameter and length. Experiments were conducted using polyvinyl chloride (PVC) tubing and results confirmed in HVAD Gelweave conduit. Conduit diameter was negatively and nonlinearly associated with mean and peak gradient in both the PVC and HVAD conduits. There were no significant differences between the PVC and HVAD conduits in terms of mean Q, systolic dQ/dt, mean conduit gradient, or peak gradient. Across the 10 mm HVAD conduit, mean gradient correlated linearly with mean Q, systolic dQ/dt, HCT, and conduit length (r = 0.91), whereas peak gradient correlated with mean Q, systolic dQ/dt, and conduit length (r = 0.93). A nonlinear model to determine instantaneous gradient was highly predictive (r = 0.83) across a range of pump and circulatory conditions. In summary, hemodynamically significant pressure gradients are observed across the LVAD outflow conduit under physiologic conditions, which may result in diminished pump flow.

Clinical Introduction: A 56-year-old lady with a background of hypertension was admitted to our institution with acute pulmonary oedema. She reported gradual and increasingly severe dyspnoea on exertion over the preceding 12 months and, prior to presentation, her exercise tolerance was restricted to one flight of stairs. On transthoracic echocardiography during the index admission, left ventricular size and systolic function were normal, and peak and mean transaortic gradients were 67 mm Hg and 33 mm Hg, respectively, with a peak velocity of 3.9 m/s. No aortic incompetence or other significant valvular abnormality was noted. A transoesophageal echocardiogram was performed. Figure 1 depicts the mid-oesophageal parasternal long-axis view. What is the explanation behind the significant transaortic gradient?heartjnl;104/12/1036/F1F1F1Figure 1Transoesophageal echocardiogram, mid-oesophageal long-axis view at 135 degrees., Question: What is the explanation behind the significant transaortic gradient?Ventricular septal defect Supravalvular aortic stenosisAortic valvular stenosisSubaortic membraneHypertrophic obstructive cardiomyopathy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Continuous-flow left ventricular assist devices (CF-LVADs) improve functional capacity in patients with end-stage heart failure. Pump output can be increased by increased pump speed as well as changes in loading conditions., Methods: The effect of exercise on invasive hemodynamics was studied in two study protocols. The first examined exercise at fixed pump speed (n = 8) and the second with progressive pump speed increase (n = 11). Patients underwent simultaneous right-heart catheterization, mixed venous saturation, echocardiography and mean arterial pressure monitoring. Before exercise, a ramp speed study was performed in all patients. Patients then undertook symptom-limited supine bicycle exercise., Results: Upward titration of pump speed at rest (by 11.6 ± 8.6% from baseline) increased pump flow from 5.3 ± 1.0 to 6.3 ± 1.0 liters/min (18.9% increase, p < 0.001) and decreased pulmonary capillary wedge pressure (PCWP; 13.6 ± 5.4 to 8.9 ± 4.1 mm Hg, p < 0.001). Exercise increased pump flow to a similar extent as pump speed change alone (to 6.2 ± 1.0 liters/min, p < 0.001), but resulted in increased right- and left-heart filling pressures (right atrial pressure [RAP]: 16.6 ± 7.5 mm Hg, p < 0.001; PCWP 24.8 ± 6.7 mm Hg, p < 0.001). Concomitant pump speed increase with exercise enhanced the pump flow increase (to 7.0 ± 1.4 liters/min, p < 0.001) in Protocol 2, but did not alleviate the increase in pre-load (RAP: 20.5 ± 8.0 mm Hg, p = 0.07; PCWP: 26.8 ± 12.7 mm Hg; p = 0.47). Serum lactate and NT-proBNP levels increased significantly with exercise., Conclusions: Pump flow increases with up-titration of pump speed and with exercise. Although increased pump speed decreases filling pressures at rest, the benefit is not seen with exercise despite concurrent up-titration of pump speed., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Background: New generation continuous-flow left ventricular assist devices (LVADs) utilise centrifugal pumps. Data concerning their effect on patient haemodynamics, ventricular function and tissue perfusion is limited. We aimed to document these parameters following HeartWare centrifugal continuous-flow LVAD (HVAD) implantation and to assess the impact of post-operative right heart failure (RHF)., Methods: We reviewed 53 consecutive patients (mean age 49.5 ± 14.1 yrs) with HVAD implanted in the left ventricle, at St. Vincent's Hospital, Sydney, between January 2007 and August 2012. Available paired right heart catheterisation (n=35) and echocardiography (n=39) data was reviewed to assess response of invasive haemodynamics and ventricular function to LVAD support., Results: A total of 28 patients (53%) were implanted from interim mechanical circulatory support. Seventeen patients (32%) required short-term post-implant veno-pulmonary artery extracorporeal membrane oxygenation. At 100 ± 61 days post-implant, mean pulmonary artery pressure and mean pulmonary capillary wedge pressure decreased from 38.8 ± 7.7 to 22.9 ± 7.7 mmHg and 28.3 ± 6.4 to 13.4 ± 5.4 mmHg respectively (p<0.001). LV end diastolic diameter decreased from 71.3 ± 12.7 to 61.1 ± 13.7 mm and LV end-systolic diameter from 62.7 ± 12.3 to 53.9 ± 14.4mm (p<0.001). Aortic regurgitation remained trivial. Serum sodium increased from 133.3 ± 5.7 to 139.3 ± 2.8 mmol/L and creatinine decreased from 109.1 ± 42.5 to 74.3 ± 26.2 μmol/L (p<0.001). Across the entire cohort, the six-month survival/transplant rate was significantly lower for RHF patients (72.2%, n=18) compared to those without (96.9%, n=35, p=0.01)., Conclusions: HVAD support improves haemodynamics, LV dimensions and renal function. Following implantation with a centrifugal continuous-flow LVAD, RHF remains a significant risk with a tendency to worse outcomes in the short to medium term., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Third-generation continuous-flow left ventricular assist devices (LVAD) provide reduced pulsatility flow. We examined the safe working range for LVAD pump speed and the effect on pump output and cardiac function in 13 stable outpatients with VentrAssist-LVAD (Ventracor Ltd, Australia). Pump speed was decreased from a baseline mean of 2,073 ± 86 revolutions per minute (RPM, with corresponding mean flow of 5.59 ± 1.18 L/min, mean ± standard deviation) to an average low-speed of 1,835 ± 55 RPM (corresponding flow 4.68 ± 0.99 L/min) and up to high-speed of 2,315 ± 66 RPM (corresponding flow 6.30 ± 1.29 L/min). There was a strong linear relationship between alteration in speed and flow rates (r(2) = 0.89, p < 0.00001) but marked interpatient variation. Downward titration to preset minimum 1,800 RPM was achieved in 9/13 (69%) and upward titration to the preset maximum 2,400 RPM was achieved in 4/13 (31%). Upward titration was stopped due to ventricular suction or nonsustained ventricular tachycardia (VT) in 4/13 (31%). Ventricular suction or VT (in 4/13) tended to be more common in patients with poor right ventricular (RV) function (p = 0.07). In summary, pump flow is stable within a relatively small speed range and should not be altered without close monitoring due to variation in response between patients, particularly with concomitant RV impairment.

Background: The aim of this study was to evaluate the efficacy of inhaled nitric oxide in the prevention and reversal of pulmonary hypertension during and after left ventricular assist device implantation., Methods: Inhaled nitric oxide (20 ppm) was administered to seven consecutive patients undergoing implantation of a left ventricular assist device at the time of implantation and for the first 24 hours after operation., Results: Withdrawal of inhaled nitric oxide at 24 hours after operation was associated with a significant rise in both the transpulmonary gradient (from 8+/-1 to 14+/-2 mm Hg, p < 0.01) and in pulmonary vascular resistance (from 110+/-19 to 196+/-32 dynes x sec x cm[-5], p < 0.01). In two patients, the rise in pulmonary vascular resistance resulted in a critical fall in left ventricular assist device flow and hemodynamic deterioration, necessitating urgent reinstitution of inhaled nitric oxide., Conclusion: The administration of inhaled nitric oxide at the time of left ventricular assist device implantation prevents rises in pulmonary vascular resistance that in some patients result in critical reductions in left ventricular assist device flow. We suggest that inhaled nitric oxide is a useful adjunctive treatment that should be routinely available at the time of left ventricular assist device implantation.

The majority of patients with continuous-flow left ventricular assist devices (cf-LVADs) experience exertional symptoms despite adequate unloading at rest. We utilized pressure-volume (PV) loops to analyze the hemodynamic effects of exercise at varying pump speeds in stable HeartWare HVAD patients. Data were obtained at baseline pump speed and +400RPM, at rest and during supine cycle ergometry to 45W. PAWP, right atrial pressure (RAP) and mean arterial pressure (MAP) were measured invasively. From derived PV loops, left ventricular end-diastolic pressure (LVEDP) and volume (LVEDV), stroke volume, stroke work (SW), and maximum derivative of left ventricular pressure (dP/dt) were calculated. We also assessed the association between exercise PAWP and admissions for hemocompatibility related adverse events (HCRE). Thirteen patients were assessed, generating 52 PV loops. Exercise significantly increased PAWP (p<0.001) and RAP (p<0.001) but not MAP (p=0.69). Increased pump speed significantly reduced PAWP at baseline (p<0.001) but not during exercise (p=0.08). The change in PAWP during exercise correlated linearly with both change in RAP (p=0.008) and change in MAP (p=0.002). PV loop analysis revealed exercise-induced increase in LVEDP (p<0.001), LVEDV (p=0.001), stroke work (p<0.001), maximum dP/dt (p=0.001), and stroke volume (p=0.007), consistent with increased preload and ventricular contraction. Patients with exercise PAWP <25mmHg had significantly higher stroke work (p=0.010) and greater change in maximum dP/dt (p=0.005) with exercise, compared to those with exercise PAWP >25mmHg. Admissions for HCRE occurred more frequently in the higher PAWP group compared to the lower PAWP group (p=0.015). Patients with optimal exercise hemodynamics under cf-LVAD support have significantly greater left ventricular contractile reserve as measured by PV loops and less admissions for HCRE. [ABSTRACT FROM AUTHOR]