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BACKGROUND: In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents. METHODS: A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity. RESULTS: Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127-- 134.5); in vitro aspirin, 124 (114.5--137); and patients on dabigatran, 131 (130.5--135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5--143.5); in vitro low-dose apixaban, 141 (138.5--142); and patients on apixaban, 140 (138--142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137--150) versus 133.5 (128.5--140) minutes, P=0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points. CONCLUSIONS: In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different. [ABSTRACT FROM AUTHOR]

Background: The incidence of atrial fibrillation (AF) is rising in the aging patients with congenital heart defects (CHD). However, studies reporting on AF in patients with CHD are scarce. The aim of this multicenter study was to examine in a large cohort of patients with a variety of CHD: (1) the age of onset and initial treatment of AF, coexistence of atrial tachyarrhythmia and (2) progression of paroxysmal to (long-standing) persistent/permanent AF during long-term follow-up.Methods and Results: Patients (n=199) with 15 different CHD and documented AF episodes were studied. AF developed at 49±17 years. Regular atrial tachycardia (AT) coexisting with AF occurred in 65 (33%) patients; 65% initially presented with regular AT. At the end of a follow-up period of 5 (0-24) years, the ECG showed AF in 81 patients (41%). In a subgroup of 114 patients, deterioration from paroxysm of AF to (long-standing) persistent/permanent AF was observed in 29 patients (26%) after only 3 (0-18) years of the first AF episode. Cerebrovascular accidents/transient ischemic attacks occurred in 26 patients (13%), although a substantial number (n=16) occurred before the first documented AF episode.Conclusions: Age at development of AF in patients with CHD is relatively young compared with the patients without CHD. Coexistence of episodes of AF and regular AT occurred in a considerable number of patients; most of them initially presented with regular AT. The fast and frequent progression from paroxysmal to (long-standing) persistent or permanent AF episodes justifies close follow-up and early, aggressive therapy of both AT and AF. [ABSTRACT FROM AUTHOR]

Background: The paucity of available hearts for transplantation means that more patients remain on durable left ventricular support for longer periods of time. The Registry to Evaluate the HeartWare Left Ventricular Assist System was an investigator-initiated multicenter, prospective, single-arm database established to collect post-Conformité Européene mark clinical information on patients receiving the HeartWare ventricular assist device system as a bridge to transplantation. This registry represents the longest multicenter follow-up of primary left ventricular assist device outcomes. Methods: Data were collected on 254 commercial implants performed between February 2009 and March 2012 from 9 centers in Europe (7) and Australia (2). Patients were followed to device explant, heart transplantation, or death. The outcomes of patients through July/August 2018 were analyzed. Summary statistics were used to describe patient demographics, adverse events, length of support, and outcomes for this extended-term cohort. Results: A total of 122 patients were on support for >2 years, and 34 patients were on support for >5 years. Twenty nine patients are still alive on support (support ranging from 1213 to 3396 days), and 23 of those are on their original HeartWare ventricular assist device system. Kaplan–Meier survival through 7 years was 51%. Through 6 years, freedom from any stroke was 82%, while freedom from severely disabling stroke was 89%. Conclusions: Low rates of heart transplant now require longer periods of left ventricular assist device support in patients. This analysis demonstrates that long-term support using a HeartWare ventricular assist device system offers survival of 51% through 7 years. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Assessment of left ventricular (LV) recovery under continuous-flow LV assist device therapy is hampered by concomitant pump support. We describe derivation of noninvasive pressure-volume loops in continuous-flow LV assist device patients and demonstrate an application in the assessment of recovery. Methods and Results: Using pump controller parameters and noninvasive arterial pressure waveforms, central aortic pressure, outflow conduit pressure gradient, and instantaneous LV pressure were calculated. Instantaneous LV volumes were calculated from echocardiographic LV end-diastolic volume accounting for the integral of pump flow with respect to time and aortic ejection volume derived from the pump speed waveform. Pressure-volume loops were derived during pump speed adjustment and following bolus intravenous milrinone to assess changes in loading conditions and contractility, respectively. Fourteen patients were studied. Baseline noninvasive LV end-diastolic pressure correlated with invasive pulmonary arterial wedge pressure (r 2=0.57, root mean square error 5.0 mm Hg, P =0.003). Measured noninvasively, milrinone significantly increased LV ejection fraction (40.3±13.6% versus 36.8±14.2%, P <0.0001), maximum dP/dt (623±126 versus 555±122 mm Hg/s, P =0.006), and end-systolic elastance (1.03±0.57 versus 0.89±0.38 mm Hg/mL, P =0.008), consistent with its expected inotropic effect. Milrinone reduced myocardial oxygen consumption (0.15±0.06 versus 0.16±0.07 mL/beat, P =0.003) and improved myocardial efficiency (43.7±14.0% versus 41.2±15.5%, P =0.001). Reduced pump speed caused increased LV end-diastolic volume (190±80 versus 165±71 mL, P <0.0001) and LV end-diastolic pressure (14.3±10.2 versus 9.9±9.3 mm Hg, P =0.024), consistent with a predictable increase in preload. There was increased myocardial oxygen consumption (0.16±0.07 versus 0.14±0.06 mL O2/beat, P <0.0001) despite unchanged stroke work (P =0.24), reflecting decreased myocardial efficiency (39.2±12.7% versus 45.2±17.0%, P =0.003). Conclusions: Pressure-volume loops are able to be derived noninvasively in patients with the HeartWare HVAD and can detect induced changes in load and contractility. [ABSTRACT FROM AUTHOR]

Background: Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting., Methods: This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up., Results: There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P = 0.08)., Conclusions: In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials., Competing Interests: J.B. is supported by National Health and Medical Research Council (NHMRC) and National Heart Foundation Post Graduate Scholarships. D.K. is supported by an NHMRC Investigator Grant. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activity. The aim of this report is to review the first 8 y of our clinical heart transplant program at St Vincent's Hospital Sydney, to describe how our program has evolved and to report the impact that changes to our retrieval protocols have had on posttransplant outcomes. Since 2014, we have performed 74 DCD heart transplants from DCD donors utilizing a direct procurement protocol followed by normothermic machine perfusion. Changes to our retrieval protocol have resulted in a higher retrieval rate from DCD donors and fewer rejections of DCD hearts during normothermic machine perfusion. Compared with our previously reported early experience in the first 23 transplants, we have observed a significant reduction in the incidence of severe primary graft dysfunction from 35% (8/23) to 8% (4/51) in the subsequent 51 transplant recipients ( P < 0.01). The only withdrawal time interval significantly associated with severe primary graft dysfunction was the asystolic warm ischemic time: 15 (12-17) versus 13 (11-14) min ( P < 0.05). One- and 5-y survival of DCD heart transplant recipients was 94% and 88%, comparable to that of a contemporary cohort of donation after brain death recipients: 87 and 81% ( P -value was not significant). In conclusion, heart transplantation from DCD donors has become a major contributor to our overall transplant activity accounting for almost 30% of all transplants performed by our program in the last 2 y, with similar DCD and donation after brain death outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Durable continuous-flow left ventricular assist devices (cfLVADs) demonstrate superior survival, cardiac functional status, and overall quality of life compared to medical therapy alone in advanced heart failure. Previous studies have not considered the impact arterial compliance may have on pump performance or developed arterial pressure. This study assessed the impact of alterations in arterial compliance, preload, and afterload on continuous-flow pump function and measured hemodynamics using an in-vitro pulsatile mock circulatory loop. Decreased arterial compliance was associated with a significant increase in arterial pressure pulsatility which was not evident in the flow pulsatility, as displayed in pump flow waveforms. There were marked changes in the pump flow waveforms due to the significant alteration in the aortoventricular gradient during diastole according to the changes in compliance. This study demonstrates that changes in systemic blood pressure, afterload, and left ventricular contractility each significantly affects the flow waveform. The association of hypertension with lower aortic compliance results in markedly decreased diastolic flow rates which may be important in contributing to a greater risk of adverse events under cfLVAD support., Competing Interests: Disclosure: C.H.: Medtronic - Speakers’ Bureau, Consultancy to individual, Research grant to Hospital, Patent Holder (owned by hospital, Licenced by Medtronic). Other authors have no conflicts of interest to disclosure., (Copyright © ASAIO 2022.)

Low flow and suction alarms are provided to alert caregivers of changes in left ventricular assist device pump function but may be reset in clinical practice. We investigated the incidence and underlying causes of these alarms as well as their prognostic significance. HeartWare ventricular assist device patients (n = 113) were divided into quartiles based on their frequency of low flow and suction alarms. Survival and adverse events (thrombus, stroke, bleeding, and right heart failure) were compared between quartiles. Low flow alarms peaked in the first few months of pump support before dropping down to near negligible levels. Suction alarm frequency remained relatively constant throughout pump support. Although pump speeds (p < 0.001) and flow (p = 0.01) decreased over time, there was an increase in suction alarm frequency (p = 0.018), with no changes in low flow alarms. Patients with smaller body size (p = 0.016) and lower pump flows (p = 0.008) had higher frequencies of low flow alarms on multiple regression (p < 0.001). Patients with the highest low flow alarm frequency demonstrated poorer survival (p = 0.026). There was no relationship between suction alarm frequency and survival. There was also no relationship between either low flow or suction alarm frequency with strokes, gastrointestinal bleeds, pump thrombus, or right ventricular failure. Duration of alarm and intervention in response to the alarm was not assessed in this study. Further studies examining alarm duration and responses may inform future pump alarm algorithms., (Copyright © ASAIO 2021.)

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.

Left ventricular assist device (LVAD) therapy has been used primarily in patients with end-stage dilated cardiomyopathy (DCM), and patients with hypertrophic cardiomyopathy (HCM) are generally excluded. We compared outcomes in 3 HCM patients with 36 DCM patients. While HCM patients had smaller left ventricular end-diastolic dimensions, average pump flows for the two groups were similar. All patients had marked improvement in mean pulmonary arterial pressures and cardiac index at 5 months. This analysis shows that patients with end-stage heart failure resulting from HCM do benefit from centrifugal cfLVAD therapy in the short to medium term.

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.