Investigation of hemodynamics in an in vitro system simulating left ventricular support through the right subclavian artery using 4-dimensional flow magnetic resonance imaging.

OBJECTIVES Left ventricular assist devices are an important treatment option for patients with heart failure alter the hemodynamics in the heart and great vessels. Because in vivo magnetic resonance studies of patients with ventricular assist devices are not possible, in vitro models represent an important tool to investigate flow alterations caused by these systems. By using an in vitro magnetic resonance-compatible model that mimics physiologic conditions as close as possible, this work investigated the flow characteristics using 4-dimensional flow-sensitive magnetic resonance imaging of a left ventricular assist device with outflow via the right subclavian artery as commonly used in cardiothoracic surgery in the recent past. METHODS An in vitro model was developed consisting of an aorta with its supra-aortic branches connected to a left ventricular assist device simulating the pulsatile flow of the native failing heart. A second left ventricular assist device supplied the aorta with continuous flow via the right subclavian artery. Four-dimensional flow-sensitive magnetic resonance imaging was performed for different flow rates of the left ventricular assist device simulating the native heart and the left ventricular assist device providing the continuous flow. Flow characteristics were qualitatively and quantitatively evaluated in the entire vessel system. RESULTS Flow characteristics inside the aorta and its upper branching vessels revealed that the right subclavian artery and the right carotid artery were solely supported by the continuous-flow left ventricular assist device for all flow rates. The flow rates in the brain-supplying arteries are only marginally affected by different operating conditions. The qualitative analysis revealed only minor effects on the flow characteristics, such as weakly pronounced vortex flow caused by the retrograde flow via the brachiocephalic artery. CONCLUSIONS The results indicate that, despite the massive alterations in natural hemodynamics due to the retrograde flow via the right subclavian and brachiocephalic arteries, there are no drastic consequences on the flow in the brain-feeding arteries and the flow characteristics in the ascending and descending aortas. It may be beneficial to adjust the operating condition of the left ventricular assist device to the residual function of the failing heart.

Aortic flow patterns resulting from right axillary artery cannulation

Right axillary artery (RAA) cannulation is increasingly used in cardiac surgery. Little is known about resulting flow patterns in the aorta. Therefore, flow was visualized and analyzed. A mock circulatory circuit was assembled based on a compliant transparent anatomical silicon aortic model. A RAA cannula was connected to a continuous flow rotary blood pump (RBP), pulsatile heart action was provided by a pneumatic ventricular assist device (PVAD). Peripheral vascular resistance, regional flow and vascular compliance were adjusted to obtain physiological flow and pressure waveforms. Colorants were injected automatically for flow visualization. Five flow distributions with a total flow of 4 l/min were tested (%PVAD:%RBP): 100:0, 75:25, 50:50, 25:75, 0:100. Colorant distribution was assessed using quantitative 2D image processing. Continuous flow from the RAA divided in a retrograde and an antegrade portion. Retro- to antegrade flow ratio increased with increasing RAA-flow. At full RBP support flow was stagnant in the ascending aorta. There were distinct flow patterns between the right- and left-sided supra-aortic branches. At full RBP support retrograde flow was demonstrated in the right carotid and right vertebral arteries. Further studies are needed to confirm and evaluate the described flow patterns.

A robust reference signal generator for synchronized ventricular assist devices

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.

Continuous flow left ventricular assist devices: a valid option for heart failure patients

Recent outstanding clinical advances with new mechanical circulatory systems (MCS) have led to additional strategies in the treatment of end stage heart failure (HF). Heart transplantation (HTx) can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVAD). Mechanical support of the failing left ventricle enables appropriate hemodynamic stabilisation and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group 0 or B, with a body weight over 90 kg and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent peri-operative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of a LVAD represents a surgical challenge. This review summarises the current knowledge about LVAD and continuous flow devices especially since the latter have been increasingly used worldwide in the most recent years. The review is also based on the institutional experience at Berne University Hospital between 2000 and 2012. Apart from short-term devices (Impella, Cardiac Assist, Deltastream and ECMO) which were used in approximately 150 cases, 85 pulsatile long-term LVAD, RVAD or bi-VAD and 44 non-pulsatile LVAD (mainly HeartMateII and HeartWare) were implanted. After an initial learning curve, one-year mortality dropped to 10.4% in the last 58 patients.

Reply to the editor

We appreciate the comments and concerns expressed by Arakawa and colleagues regarding our article, titled “Pulsatile control of rotary blood pumps: Does the modulation waveform matter?”1 Unfortunately, we have to disagree with Arakawa and colleagues. As is obvious from the title of our article, it investigates the effect of different waveforms on the heart–device interaction. In contrast to the authors' claim, this is the first article in the literature that uses basic waveforms (sine, triangle, saw tooth, and rectangular) with different phase shifts to examines their impact on left ventricular unloading. The previous publications2, 3 and 4 just varied the pump speed during systole and diastole, which was first reported by Bearnson and associates5 in 1996, and studied its effect on aortic pressure, coronary flow, and end-diastolic volume. We should mention that dp/dtmax is a load-sensitive parameter of contractility and not representative for the degree of unloading. Moreover, none of the aforementioned reports has studied mechanical unloading and in particular the stroke work of the left ventricle. Our method is unique because we do not just alternate between high and low speed but have accurate control of the waveform because of the direct drive system of Levitronix Technologies LLC (Waltham, Mass) and a custom-developed pump controller. Without referring, Arakawa and associates state “several previous studies have already reported the coronary flow diminishes as the left ventricular assist device support increases.” It should be noted that all the waveforms used in our study have 2000 rpm average value with 1000 rpm amplitude, which is not an excessive speed for the CentriMag rotary pump (Levitronix) to collapse the ventricle and diminish the coronary flow. We agree with Arakawa and coworkers that there is a need for a heart failure model to come to more relevant results with respect to clinical expectations. However, we have explored many existing models, including species and breeds that have a native proneness to cardiomyopathy, but all of them differ from the genetic presentation in humans. We certainly do not believe that the use of microembolization, in which the coronary circulation is impaired by the injection of microspheres, would form a good model from which to draw conclusions about coronary flow change under different loading conditions. A model would be needed in which either an infarct is created to mimic ischemic heart failure or the coronary circulation remains untouched to simulate, for instance, dilated cardiomyopathy. Furthermore, in discussion we clearly mention that “lack of heart failure is a major limitation of our study.” We also believe that unloading is not the only factor of the cardiac functional recovery, and an excessive unloading of the left ventricle might lead to cardiac tissue atrophy. Therefore, in our article we mention that control of the level of cardiac unloading by assist devices has been suggested as a mechanical tool to promote recovery, and more studies are required to find better strategies for the speed modulation of rotary pumps and to achieve an optimal heart load control to enhance myocardial recovery. Finally, there are many publications about pulsing rotary blood pumps and it was impossible to include them all. We preferred to reference some of the earlier basic works such as an original research by Bearnson and coworkers5 and another article published by our group,6 which is more relevant.

A novel interface for hybrid mock circulations to evaluate ventricular assist devices

This paper presents a novel mock circulation for the evaluation of ventricular assist devices (VADs), which is based on a hardware-in-the-loop concept. A numerical model of the human blood circulation runs in real time and computes instantaneous pressure, volume, and flow rate values. The VAD to be tested is connected to a numerical-hydraulic interface, which allows the interaction between the VAD and the numerical model of the circulation. The numerical-hydraulic interface consists of two pressure-controlled reservoirs, which apply the computed pressure values from the model to the VAD, and a flow probe to feed the resulting VAD flow rate back to the model. Experimental results are provided to show the proper interaction between a numerical model of the circulation and a mixed-flow blood pump.

Pulsatile control of rotary blood pumps: Does the modulation waveform matter?

Mechanical support of a failing heart is typically performed with rotary blood pumps running at constant speed, which results in a limited control on cardiac workload and nonpulsatile hemodynamics. A potential solution to overcome these limitations is to modulate the pump speed to create pulses. This study aims at developing a pulsatile control algorithm for rotary pumps, while investigating its effect on left ventricle unloading and the hemodynamics.

Percutaneous ventricular assist devices for cardiogenic shock

Cardiogenic shock complicates up to 7% of ST-segment elevation myocardial infarctions and 2.5% of non-ST-segment elevation myocardial infarctions, with an associated mortality of 50% to 70%. Primary cardiac pump failure is followed by secondary vital organ hypoperfusion and subsequent activation of various cascade pathways, resulting in a downward spiral leading to multiple organ failure and, ultimately, death. Immediate restoration of cardiac output by means of percutaneous ventricular assist devices restores hemodynamic -stability and is an important advance in the management of patients with severe left ventricular dysfunction and cardiogenic shock. This article reviews available evidence supporting the use of percutaneous ventricular assist devices in patients suffering from cardiogenic shock.

Mechanical circulatory support as a bridge to heart transplantation: what remains? Long-term emotional sequelae in patients and spouses

Implantation of a ventricular assist device (VAD) reduces short-term mortality and morbidity and provides patients with reasonable quality of life even though it may also be a long-lasting emotional burden. This study was conducted to analyze the long-time emotional consequences of VAD implantation, followed by heart transplantation in patients and spouses.

Acute device-based blood pressure reduction: electrical activation of the carotid baroreflex in patients undergoing elective carotid surgery

Carotid sinus baroreceptors are involved in controlling blood pressure (BP) by providing input to the cardiovascular regulatory centers of the medulla. The acute effect of temporarily placing an electrode on the carotid sinus wall to electrically activate the baroreflex was investigated. We studied 11 patients undergoing elective carotid surgery. Baseline BP was 146+30/66+/-17 mm Hg and heart rate (HR) 72+/-7 bpm (mean +/- standard deviation). An electrode was placed upon the carotid sinus and after obtaining a steady state baseline of BP and HR, an electric current was applied and increased in 1-volt increments. A voltage dependent and highly significant reduction in BP was observed which averaged 18+/-26* and 8.0+/-12 mm Hg for systolic BP and diastolic BP, respectively. Maximal reductions occurred at 4.4+/-1.2 V: 23+/-24 mm Hg*, 16+/-10 mm Hg* and 7+/-12 bpm* for systolic BP, diastolic BP and HR, respectively ( = p <.05). Thus, electrical stimulation of the carotid sinus activates the carotid baroreflex resulting in a reduction in BP and HR. This presents a proof of concept for device based baroreflex modulation in acute BP regulation and adds to the available data which provide a rationale for evaluating this system in the context of chronic BP reduction in hypertensive patients.

Aquatic therapies in patients with compromised left ventricular function and heart failure

With water immersion, gravity is partly eliminated, and the water exerts a pressure on the body surface. Consequently there is a blood volume shift from the periphery to the central circulation, resulting in marked volume loading of the thorax and heart. This paper presents a selection of published literature on water immersion, balneotherapy, aqua exercises, and swimming, in patients with left ventricular dysfunction (LVD) and/or stable chronic heart failure (CHF). Based on exploratory studies, central hemodynamic and neurohumoral responses of aquatic therapies will be illustrated. Major findings are: 1. In LVD and CHF, a positive effect of therapeutic warm-water tub bathing has been observed, which is assumed to be from afterload reduction due to peripheral vasodilatation caused by the warm water. 2. In coronary patients with LVD, at low-level water cycling the heart is working more efficiently than at lowlevel cycling outside of water. 3. In patients with previous extensive myocardial infarction, upright immersion to the neck resulted in temporary pathological increases in mean pulmonary artery pressure (mPAP) and mean pulmonary capillary pressures (mPCP). 4. Additionally, during slow swimming (20-25m/min) the mPAP and/or PCP were higher than during supine cycling outside water at a 100W load. 5. In CHF patients, neck- deep immersion resulted in a decrease or no change in stroke volume. 6. Although patients are hemodynamically compromised, they usually maintain a feeling of well-being during aquatic therapy. Based on these findings, clinical indications for aquatic therapies are proposed and ideas are presented to provoke further research.

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.

Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

AIMS Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION NCT00769678.