Quantification of pulsatility as a function of vascular input impedance: an in vitro study

The physiological benefits of pulsatility generated by ventricular assist device (VAD) support continue to be heavily debated as application of VAD support has been expanded to include destination and recovery therapies. In this study, the relationship between input impedance (Zart) and vascular pulsatility during continuous flow (CF) or pulsatile flow (PF) VAD support was investigated. Hemodynamic waveforms were recorded at baseline failure and with 50%, 75%, and 100% CF or PF VAD support for nine different Zart test conditions (combination of three different resistance and compliance settings) in a mock circulatory system simulating left ventricular failure. High-fidelity hemodynamic pressure and flow waveforms were recorded to calculate mean arterial pressure (MAP), Zart, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) as metrics for quantifying vascular pulsatility. MAP and EEP were elevated with increasing resistance whereas SHE was reduced with increasing compliance. Vascular pulsatility was restored with increasing PF VAD support, but diminished by up to 90% with increasing CF VAD support. The nonpulsatile energy component (MAP) of the pressure waveform is dependent on resistance whereas the pulsatile energy component (SHE) is dependent on compliance. The impact of Zart and vascular pulsatility on patient recovery with VAD support warrants further investigation.     

Effect of continuous and pulsatile flow left ventricular assist on pulsatility in a pediatric animal model of left ventricular dysfunction: pilot observations

Pediatric ventricular assist devices are being developed that can produce pulsatile flow (PF) or continuous flow (CF). An important aspect of choosing between these two modes is understanding the consequences of each mode on pediatric vascular pulsatility. Differences in vascular pulsatility generated by PF and CF operation of the 3-inch pediatric cardiopulmonary assist system (pCAS, Ension, Inc., Pittsburgh, PA) were investigated while providing left atrium-to-aorta left ventricular assist (LVA), using an infant animal model of left ventricular dysfunction. Hemodynamic data were digitally recorded with the pCAS providing LVA at incremental flow rates while operating in continuous mode, pulsatile mode at 100 bpm, and pulsatile mode at 140 bpm. These data were used to calculate vascular input impedance (Zart), energy equivalent pressure, and surplus hemodynamic energy as indices of pulsatility for partial (50% of maximum) and maximum LVA flow. Both CF and PF LVA by the pCAS resulted in favorable hemodynamic rectification of left ventricular dysfunction while generating equivalent flows. PF LVA maintained a greater degree of pulsatility compared with CF, as evidenced by increasing energy equivalent pressure and a lesser drop in surplus hemodynamic energy with increasing pCAS flow. Differences in Zart modulus and phase were indiscernible. The selection of flow mode may have long-term consequences on Zart and end-organ perfusion affecting clinical outcomes in pediatric patients.     

Successful combined use of Impella Recover 2.5 device and intra-aortic balloon pump support in cardiogenic shock from acute myocardial infarction

Ventricular assist devices (VADs) and intra-aortic balloon pumps (IABPs) are important tools that provide hemodynamic support to patients in cardiogenic shock. The Impella Recover 2.5 is a percutaneous VAD that provides temporary circulatory support. We report the case of a patient who required the combined support of both an IABP and the Impella device.     

Left ventricular and myocardial perfusion responses to volume unloading and afterload reduction in a computer simulation

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. In a few cases, patients have been successfully weaned from these devices after myocardial recovery. To promote myocardial recovery and alleviate the demand for donor organs, we are developing an artificial vasculature device (AVD) that is designed to allow the heart to fill to its normal volume but eject against a lower afterload. Using this approach, the heart ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which has been programmed to produce any desired afterload condition defined by an input impedance profile. During diastole, the AVD returns this SV to the aorta, providing counterpulsation. Dynamic computer models of each of the assist devices (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model of the cardiovascular system. Computer simulations of these assist techniques were conducted to predict physiologic responses. Hemodynamic parameters, ventricular pressure-volume loops, and vascular impedance characteristics were calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a range of clinical cardiac conditions (normal, failing, and recovering left ventricle). These simulation results indicate that the AVD may provide better coronary perfusion, as well as lower vascular resistance and elastance seen by the native heart during ejection compared with continuous and pulsatile VAD. Our working hypothesis is that by controlling afterload using the AVD approach, ventricular cannulation can be eliminated, myocardial perfusion improved, myocardial compliance and resistance restored, and effective weaning protocols developed that promote myocardial recovery.     

Axial flow blood pumps

Each year, thousands of cardiac patients await healthy donor hearts for transplantation. Due to the current shortage of donor hearts (approximately 2300 per year), these patients often require supplemental circulatory support until a transplant becomes available. This supplemental support is often provided by a mechanical heart pump or left ventricular assist device (LVAD). This article explores one type of LVAD, specifically the design and development of axial flow ventricular assist devices (VAD). We discuss the design details, and experimental or clinical experience with the following axial flow support systems: Hemopump, MicroMed DeBakey VAD, Jarvik 2000, HeartMate II, Streamliner, Impella, Berlin INCOR I, Valvo pump, and IVAP. All of these devices demonstrate promise in providing bridge-to-transplant and ultimately destination therapy for adult cardiac failure patients.     

Pediatric mechanical circulatory support in the United States: past, present, and future

Mechanical support of the failing myocardium has become standard therapy for adults who fail medical management. Historically, there have been fewer options for children with heart failure. Extracorporeal membrane oxygenation and centrifugal pump-based ventricular assist devices have been the most commonly used circulatory support modalities for pediatrics in the United States. During the last few years, substantial advances in pediatric circulatory support have been made, with greater availability of a number of devices suitable for pediatrics. For example, there has been increasing experience using the DeBakey VAD Child and the Berlin Heart VAD to provide circulatory support for children during this period. A number of innovative devices under development supported by the Pediatric Circulatory Support Program of the National Heart, Lung, and Blood Institute hold great promise for expanded options for pediatric mechanical circulatory support in the future.     

Early in vivo experience with the pediatric Jarvik 2000 heart

The need for smaller, more efficient ventricular assist devices that can be used in a more chronic setting have led to exploration of mechanical circulatory support in the pediatric population. The pediatric Jarvik 2000 heart (child size), under development, was implanted in six juvenile sheep and studied for both acute fit and chronic performance evaluation. Daily hemodynamic measurements of cardiac output and pump output at varying pump speeds were taken. In addition, plasma free hemoglobin, lactic acid dehydrogenase, and platelet activation from blood samples were determined at baseline, after implantation, and twice a week thereafter. The measured flow through the outflow graft at increasing speeds from 10,000 rpm to 14,000 rpm with an increment of 1,000 rpm were 1.47 +/- 0.43, 1.89 +/- 0.52, 2.36 +/- 0.61, 2.80 +/- 0.73, and 3.11 +/- 0.86 (L/min). The baseline plasma free hemoglobin was 11.95 +/- 4.76 (mg/dL), with subsequent mean values being <30 mg/dL at postimplantation and weekly postimplantation measurements. Both lactic acid dehydrogenase and platelet activation showed an acute increase within the first week after implantation with subsequent return to baseline by 2 weeks after surgery. Our initial animal in vivo experience with the pediatric Jarvik 2000 heart shows that a small axial flow pump can provide partial to nearly complete circulatory support with minimal adverse effects on blood components.     

Pediatric circulatory support systems

Ventricular assist devices (VADs) are a valid option for long term circulatory support in pediatric patients with postoperative myocardial failure or debilitating heart defects. Most clinical experience to date has involved the short-term support of patients weighing 6 kg and larger. For cases of VAD implementation in pediatric patients, the assist device showed tremendous promise in reversing cardiac failure and providing adequate support as a bridge to cardiac transplantation. The Medos-HIA system, Berlin Heart, Medtronic Bio-Medicus Pump, Abiomed BVS 5000, Toyobo-Zeon pumps, and Hemopumps have proven successful for short-term circulatory support for the pediatric population. The Jarvik 2000 and Pierce-Donachy pediatric system further demonstrate the potential to be used for pediatric circulatory support. The clinical and experimental success of these support systems provide encouragement to believe that long-term support is possible.     

Engineering analysis of the effects of bulging sinuses in a newly designed pediatric pulmonary heart valve on hemodynamic function

The purpose of this study was to examine the hemodynamic characteristics of expanded polytetrafluoroethylene (ePTFE) pulmonary valves with bulging sinuses quantitatively in a pediatric pulmonary mechanical circulatory system designed by us, in order to propose the optimal design for clinical applications. In this study, we developed a pediatric pulmonary mock circulation system, which consisted of a pneumatic right ventricular model, a pulmonary heart valve chamber, and a pulmonary elastic compliance tubing with resistive units. The hemodynamic characteristics of four different types of ePTFE valves and a monoleaflet mechanical heart valve were examined. Relationships between the leaflet movements and fluid characteristics were evaluated based on engineering analyses using echocardiography and a high-speed video camera under the pediatric circulatory conditions of the mock system. We successfully performed hemodynamic simulations in our pediatric pulmonary circulatory system that could be useful for quantitatively evaluating the pediatric heart valves. In the simulation study, the ePTFE valve with bulging sinuses exhibited a large eddy in the vicinity of the leaflets, whereas the straight tubing exhibited turbulent flow. The Reynolds number obtained in the valve with bulging sinuses was calculated to be 1667, which was smaller than that in the straight tubing (R (e) = 2454).The hemodynamic characteristics of ePTFE pediatric pulmonary heart valves were examined in our mock circulatory system. The presence of the bulging sinuses in the pulmonary heart valve decreased the hydrodynamic energy loss and increased the systolic opening area. Based on an in vitro experiment, we were able to propose an optimal selection of pulmonary valve design parameters that could yield a more sophisticated pediatric ePTFE valve shape.     

Comparison of pulsatile with nonpulsatile mechanical support in a porcine model of profound cardiogenic shock

The aim of this study was to examine whether pulsatility by intraaortic balloon counterpulsation (IABP) is an important adjunct to the treatment of profound cardiogenic shock (CS) with a widely used, nonpulsatile centrifugal pump (CP). In each of 18 anesthetized, open chest pigs, the outflow cannula of the CP was inserted in the aortic arch through the right external carotid artery, and the inflow cannula of the CP was placed in the left atrium. A 40 cc IABP was subsequently placed in the descending aorta through the left external carotid artery. CS was induced by occlusion of coronary arteries and the infusion of propranolol and crystalloid fluid. Mean aortic pressure, pulse pressure, aortic end diastolic pressure, left ventricular end diastolic pressure, right atrial pressure, and heart rate were monitored. Cardiac output and left anterior descending artery flow were measured with a transit time ultrasound flowmeter. During profound CS, life sustaining hemodynamics were maintained only with the support of the assist devices. Hemodynamic support with the CP was associated with a nearly nonpulsatile flow and a pulse pressure of 7 +/- 4 mm Hg, which increased to 33 +/- 10 mm Hg (p = 0.000) after combining the CP with the IABP. Compared with the hemodynamic support offered by the CP alone, addition of the IABP increased mean aortic pressure from 40 +/- 15 to 50 +/- 16 mm Hg (p = 0.000), cardiac output from 810 +/- 194 to 1,200 +/- 234 ml/min (p = 0.003), and left anterior descending artery flow from 26 +/- 10 to 39 +/- 14 ml/min (p = 0.001). In profound CS, mechanical support provided by a continuous flow CP is enhanced by the added pulsatility of the IABP.     

Current state-of-the-art of device therapy for advanced heart failure

Heart failure remains one of the most common causes of morbidity and mortality worldwide. The advent of mechanical circulatory support devices has allowed significant improvements in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of past and current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support.Heart failure is one of the most common causes of morbidity and mortality in the United States and worldwide. Although transplantation is the gold standard for end-stage heart failure, it is limited by donor supply. In the United States, about 50 000 patients die each year from heart failure but the number of heart transplants remains steady at about 2000 per year (1). Moreover, transplantation is often not optimal or feasible for instances where short-term support may be adequate. While the mainstay of treatment of heart failure has traditionally been medical optimization, non-transplant surgical interventions have grown to play a key role in the care of these patients. Mechanical circulatory support (MCS) options have grown exponentially since the first reports in the mid-twentieth century and are now considered a well-defined and accepted part of heart failure treatment strategies. These surgical procedures comprise an increasingly important part of the armamentarium of the modern cardiac surgeon.Our intent in this review is to provide a targeted overview of the currently available options for device therapy for heart failure. While the entire spectrum of MCS is quite broad and includes techniques such as intra-aortic balloon pump counterpulsation (IABP), and extracorporeal membrane oxygenation (ECMO), we will focus our discussion on ventricular assist devices (VAD) and total artificial heart (TAH) for the adult population.     

Mechanical support of the left ventricle in ischemia induced left ventricular failure: an experimental study.

OBJECTIVE: this study compares the hemodynamic effects of intra-aortic balloon pumping (IABP), left ventricular assist device (LVAD), and extracorporeal membrane oxygenation (ECMO) in left ventricular failure in pigs. METHODS: In 29 pigs weighing 12 +/- 0.7 kg left ventricular failure was induced by ligating the left anterior descending coronary artery. Eight animals served as controls. Eight pigs were treated by IABP, seven by LVAD, and six by ECMO. The study period lasted four hours. Hemodynamic and oxygen transport/uptake parameters were measured continuously or intermittently. RESULTS: Six animals of the ECMO and LVAD groups survived the 4 hour period, but only 3 and 4 animals of the IABP and control groups survived (p less than 0.05). Cardiac index decreased about 48% and 22% in the control and IABP groups (p less than 0.05), whereas there was only a slight decrease in the ECMO (9%) and LVAD (14%) groups. Oxygen delivery fell significantly in the control and IABP groups (p less than 0.05), compared with only a slight change in the LVAD and ECMO groups. CONCLUSION: ECMO is the most effective system for temporary circulatory support in severe ventricular failure. LVAD maintains cardiac output when pulmonary blood flow is provided. IABP is less efficient in supporting the failing heart, especially in the presence of severe ventricular arrhythmias.     

In vitro evaluation of the PUCA II intra-arterial LVAD

The "pulsatile catheter" (PUCA) pump is a minimally invasive intra-arterial left ventricular assist device intended for acute support of critically ill heart failure patients. To assess the hydrodynamic performance of the PUCA II, driven by an Arrow AutoCat IABP driver, we used a (static) mock circulatory system in which the PUCA II was tested at different loading conditions. The PUCA II was subsequently introduced in a (dynamic) cardiovascular simulator (CVS) to mimic actual in vivo operating conditions, with different heart rates and 2 levels of left ventricular (LV) contractility. Mock circulation data shows that PUCA II pump performance is sensitive to afterload, pump rate and preload. CVS data demonstrate that PUCA II provides effective LV unloading and augments diastolic aortic pressure. The contribution of PUCA II to total flow is inversely related to LV contractility and is higher at high heart rates. We conclude that, with the current IABP driver, the PUCA II is most effective in 1:1 mode in left ventricles with low contractility.     

IABP assistance: a test bench for the analysis of its effects on ventricular energetics and hemodynamics.

IABP assistance is frequently used to support heart recovery, improving coronary circulation and re-establishing the balance between oxygen availability and consumption. Hemodynamic and energetic parameters (endocardial viability ratio, ventricular energetics) are used to evaluate its effectiveness which depends on internal (timing, balloon volume and position) and external factors (circulatory conditions). Considering short, medium and long-term effects of IABP, the first depends on its mechanical action, the latter on the changes induced in circulatory parameters. The analysis of the first is important because conditions for the onset of a virtuous cycle able to support ventricular recovery are created. Simulation systems could be helpful in this analysis for the implicit reliability and reproducibility of the experiments, provided that they are able to reproduce both hemodynamic phenomena and energetic relationships. The aim of this paper is to present a system originally developed to test mechanical heart assist devices and modified for IABP testing. Data reported here are obtained from in vitro experiments. A partial verification, obtained from the literature is presented.     

Successful treatment of near-fatal fulminant myocarditis using bi-ventricular assist device support

Fulminant myocarditis is a rare but fatal serious disease that may cause prolonged native cardiac dysfunction with multiorgan failure despite temporary mechanical circulatory support with percutaneous venoatrial extracorporeal membrane oxygenation (VA-ECMO) or intraaortic balloon pumping (IABP). A 26-year-old man with fulminant myocarditis developed life-threatening multiorgan failure after 8 days support by VA-ECMO and IABP. He was transferred to our institution with prolonged cardiac dysfunction on hospital day 8; massive pulmonary edema developed into severe pulmonary dysfunction. Immediately after admission, VA-ECMO and IABP were switched to a paracorporeal pneumatic left ventricular assist device (LVAD) and right centrifugal ventricular assist device with an ECMO circuit shunting from the right ventricle to the pulmonary artery (RVAD-ECMO). After intensive care focusing on respiratory dysfunction, ECMO was successfully weaned, and the right ventricular assist device was switched to a durable paracorporeal pneumatic right ventricular assist device. The paracorporeal bi-ventricular assist devices were finally replaced with an implantable non-pulsatile LVAD on hospital day 181. Currently, 1 year after discharge, the patient is at home awaiting heart transplantation. Combined LVAD and RVAD-ECMO appear to be useful for resolving severe pulmonary edema due to unnecessarily long VA-ECMO support as well as kidney or liver dysfunction caused by circulatory collapse.     

The effect of aortic valve incompetence on the hemodynamics of a continuous flow ventricular assist device in a mock circulation

There is evidence that the incidence of aortic valve incompetence (AI) and other valvular pathologies may increase as more patients are submitted to longer periods of ventricular assist device (VAD) support. There is a need to better understand the mechanisms associated with the onset of these conditions and other possible complications related to the altered hemodynamics of VAD patients. In this study, the effect of AI on the hemodynamic response of continuous flow VAD (C-VAD) patients was measured in a mock loop over a range of pump speeds and level of native cardiac function. Our results showed that, in the presence of sufficient ventricular function, decreasing the C-VAD speed can allow a transition from series to parallel flow. Our study demonstrated that AI reduces the aortic pressure and flow when system impedance is unchanged. AI produces wasteful recirculation that substantially increases the pump work and decreases systemic perfusion, in particular during series flow conditions coupled with higher C-VAD speeds. The hematologic consequence of this regurgitant flow is a much higher exposure to shear for the blood, increasing the likelihood of hemolysis and thrombosis. While a certain degree of AI can be tolerated by a heart with good cardiac function, the consequences of AI for patients with VADs and poor cardiac function are much greater. Valve dysfunction in VAD patients may be related to structural changes in the tissue induced by altered biomechanics and excessive stress.     

Current circulatory support with step-by evaluation of biventricular and pulmonary function

The purpose of this study was to examine the clinical results of current circulatory support with step-by evaluation of biventricular and pulmonary function. Six patients who had undergone cardiac surgery and two non-cardiotomy patients underwent current circulatory support with the step-by functional evaluation. Of six postcardiotomy patients, four patients with severe ischemic heart disease underwent coronary artery bypass giafting (CABG), and the remaining two patients with advanced aortic stenosis underwent aortic valve replacement (AVR). All six patients received intra-aortic balloon pump (IABP) support before or during operation. Two non-cardiotomy patients suffered from dilated cardiomyopathy, and both showed acute deterioration with cardiogenic shock or low cardiac output syndrome. Three of six postcardiotomy patients with circulatory support were weaned and discharged from the hospital. Two noncardiotomy patients in critical condition were successfully supported for more than 6 months by the Novacor left ventricular assist system (LVAS). We conclude that the ongoing current strategy of circulatory support with step-by functional evaluation might be applied for various types of severe heart failure with or without associated cardiac operations.     

Total heart replacement with dual centrifugal ventricular assist devices

In an ovine feasibility study, we implanted two HeartMate-III centrifugal ventricular assist devices (VADs) for total heart replacement. With cardiopulmonary bypass support, both ventricles were transected at the atrioventricular groove, preserving a rim of ventricular tissue. The atrioventricular valves were excised, and the aorta and pulmonary artery were transected above the ventriculoarterial valves. An interatrial septal window was created by excising the foramen ovale. The VADs' sewing rings were attached to the left and right ventricular remnants, respectively. Outflow grafts were anastomosed to the aorta and pulmonary artery. The left VAD operated continuously at 4,500 rpm. Right VAD speed increased from 2,000 to 4,500 rpm in 500 rpm increments. Outflow graft flow, pressure, oxygen saturation, and shunt direction were recorded. The pulmonary artery to aortic ratio of flow and pressure increased from 0.26 and 0.15 (at 2,000 rpm) to 1.21 and 0.53, respectively (at 4,500 rpm). The interatrial shunt, which was right to left at lower right VAD speeds, progressed to bidirectional, then to left dominant as right VAD speed increased. Outflow-graft oxygen saturation was reflective of the shunt direction. In this acute experiment, total heart replacement with continuous flow VADs satisfactorily balanced left and right ventricular flows and preserved the physiologic circulatory response.     

Use of mechanical circulatory support in pediatric patients with acute cardiac graft rejection

Patients suffering from acute cardiac graft rejection can die because of hemodynamic collapse while being treated with vigorous immunosuppressive therapies. There is little pediatric data on the use of mechanical circulatory support (MCS) in patients with acute cardiac graft rejection accompanied by hemodynamic instability. This report reviews our experience using MCS in patients with severe acute allograft rejection and cardiogenic shock. Between July 1995 and December 2006, 7 of 117 heart transplant recipients (6%) had MCS placed in 8 cases of acute graft rejection with hemodynamic instability. Devices used were BioMedicus (five), Thoratec (two), and extracorporeal membrane oxygenation machine (one). Mean age was 12 +/- 6.6 years. Median duration of support was 7.5 days (range, 3-28 days). Medical therapy applied included pulse steroids (eight), antithymocyte globulin (five), intravenous immunoglobulins (five), and plasmapheresis (five). Eighty-eight percent (seven of eight cases) weaned from MCS. Five patients weaned to recovery and two were bridged to retransplant. Five of the seven patients weaned (71%) were discharged home, all with normal left ventricular function. Median follow-up was 3.0 years (4.5 months to 3.5 years). One-year survival is 50% and 3 year survival is 38%. Mechanical circulatory support can be applied in patients with acute cardiac graft rejection causing hemodynamic instability with acceptable weaning and discharge rates. Unfortunately, late survival for this cohort remains poor.     

Heart transplantation in children after mechanical circulatory support: comparison of heart transplantation with ventricular assist devices and elective heart transplantation

Heart transplantation (HTx) is an ultimate treatment for children with end-stage heart failure or inoperable congenital heart disease. The supply of hearts is inadequate; therefore, different mechanical support systems must be used as bridge to HTx in pediatric patients with postoperative low output. The use of ventricular assist devices (VADs) as bridge to HTx in children is limited because of size differences. The purpose of this study was to evaluate the overall long-term outcome of pediatric circulatory support before pediatric HTx. From 1989 through 2004, 91 pediatric patients underwent isolated HTx. Seven of them required mechanical support before transplantation. We reviewed retrospectively the course of 91 children (mean age 14.7 years) who underwent HTx. Group A consisted of elective HTx patients who were treated as outpatients before HTx, whereas group B was the VAD-HTx bridging group (n=7; mean age 12.31 +/- 2.8 years). Mean duration of VAD support was 108 +/- 98 days (minimum 1 day, maximum 258 days). Overall survival rate after HTx was 80% at 1 year without significant differences between groups. Five of seven patients survived and could be discharged after successful HTx, for a survival rate of 77%. The mean follow-up period was 16.76 +/- 10.6 months. No differences in posttransplantation long-term survival and rejection episodes occurred between patients transplanted with or without VAD. VAD therapy can keep pediatric patients with end-stage heart failure alive until successful HTx, and bridge to HTx is a safe procedure in pediatric patients. After HTx, survival rates of these children are similar to those of patients awaiting elective HTx.