Pratt, Alexandra K. MD1; Shah, Nimesh S. MD1; Boyce, Steven W. MD2
Heart failure develops in one in five Americans over age 40; nearly 50% die 5 years after the diagnosis is made (1, 2). In whom end-stage or advanced heart failure develops, nearly 70% will die or be hospitalized in 1 year (3).
Cardiac transplantation is the definitive long-term treatment for end-stage heart failure (4). However, there are insufficient heart allografts available. In 1994, the U.S. Food and Drug Administration (FDA) approved the first-generation pulsatile left ventricular assist devices (LVAD) as a bridge to transplant (BTT) for patients on waiting list and then later for patients not eligible for heart transplantation as destination therapy (DT). Newer generation continuous-flow LVADs designed for less mechanical wear doubled 2-year survival compared with pulsatile LVADs and improved quality of life for BTT and DT patients (5–7). Currently, 2-year survival at greater than 80% for patients with new generation continuous-flow LVADs rivals heart transplantation (8, 9).
With over 4,000 mechanical circulatory support devices implanted since 2006 and more readmissions after index hospitalization, intensivists will surely encounter these patients in the future (9, 10). Management of these patients requires understanding of the principles, indications, and limitations of this unique technology. This review highlights the physiology of patients with continuous-flow devices, the perioperative course, and management of common complications relevant to the critical care physician. Pulsatile intracorporeal LVADs are rarely implanted and will not be discussed.
The durable implantable continuous-flow LVADs currently in use share the same basic design and components. Each requires an inlet cannula positioned into the left ventricular (LV) apex, a pump, an outflow graft into the ascending aorta (descending aorta in the Jarvik 2000), and a controller with battery pack. HeartMate II (HMII) produced by Thoratec is the most used implantable device worldwide and the only device that is currently approved by the FDA for both BTT and DT (11, 12). In this axial flow device, a titanium corkscrew impeller with an internal magnet is supported by bearings at either end (Fig. 1). A magnetic field rotates the impeller between 6,000 and 15,000 revolutions/min (RPM) providing blood flow along the axial plane continuously during the cardiac cycle. At 100 mm Hg pressure, it provides up to 10 L/min flow (12–15). Other axial flow devices include Jarvik 2000, and the previously used Incor and MicroMed DeBakey (16–19).
Of the centrifugal flow implantable pumps, HeartWare (HW) is the only FDA-approved device for BTT. Its wide-blade impeller with magnetic elements levitates friction free by passive magnetic force and hydrodynamic thrust (Fig. 2). An electromagnetic field spins the impeller from 1,800 to 4,000 RPM and provides up to 10 L/min blood flow. In contrast to HMII, it is small enough to implant in the pericardial space (Fig. 3). The driveline is also smaller and more flexible (20–22).
The system controller is the user interface for the LVAD. It controls the LVAD motor power and speed, performs diagnostic assessment, records and stores data, indicates battery fuel levels, and alerts the user to advisory and hazard alarms. The system controller connects the two batteries to the driveline and clips to the patient’s belt (Figs. 3 and 4). A larger system monitor is used in the inpatient setting to display power, flow, speed, and pulsatility data for clinicians. Two batteries power the device for approximately 3 hours under normal conditions. Patients can be attached to the power base unit rather than batteries for extended periods of time.
As with any percutaneous device, the driveline is at risk of infection and must be handled with sterile technique. Patients and caregivers are trained in maintenance of the driveline and perform dressing changes with sterile supplies.
SURGICAL AND DEVICE IMPLANTATION
Most implantations are performed using a similar technique. The heart is accessed by median sternotomy, although thoracotomy and subcostal approaches are also described (23, 24). Patients with prior sternotomy experience longer cardiopulmonary bypass time and more bleeding (25). Dense adhesions can make dissection more difficult and dangerous for future reentry for device exchange or transplantation (26, 27). A pump pocket for HMII is created in the preperitoneal space of the upper abdomen (Fig. 4). The inflow is inserted into the apex of the LV, directed toward the mitral valve. Outflow graft is sutured to the ascending aorta. The drivelines in both HMII and HW are tunneled subcutaneously in the abdomen. Once the system is vented of air, the LVAD is initiated. Optimal pump speed is determined under transesophageal echocardiographic guidance, by septal position, right ventricular (RV) size, and function.
Pump speed (as RPM) is the only variable programmed by the operator. The other variables, power, flow, and pulsatility, displayed by the machine depend on the patient’s underlying physiology. Pump power is a direct measurement of watts required by the device to pump blood at the set RPM. Pump power correlates well with blood flow, but there are exceptions (20, 28, 29) (Table 1).
Blood flow displayed on the LVAD monitor is calculated based on measured pump power and set pump speed. For HW, blood viscosity has a significant impact on flow, and thus, hematocrit is also integrated into its algorithm (20, 21). Calculated flows have been shown to be inaccurate with the HMII at pump speeds less than or equal to 8,000 RPM (12).
The actual blood flow through the pump is dependent on the pump speed and the pressure differential, also known as head pressure, across the pump. For a fixed speed, the difference in mean aortic pressure (i.e., afterload), and LV chamber pressure (i.e., preload), correlates inversely with blood flow (Fig. 5) (13, 20, 28). The greatest determinant of the pump differential pressure is LV intracavitary pressure (22). Increased vascular tone (i.e., afterload) can also decrease pump flow (30, 31). In states of increased cardiac activity such as exercise, pump flow increases even at fixed speed due to decreased systemic vascular resistance and decreased pump differential pressure during systole (32, 33). The calculated blood flow may underestimate total cardiac output as it does not account for blood ejected by the native LV across the aortic valve (34, 35).
On physical examination, patients with continuous-flow devices may not have palpable pulses. However, contraction of the native ventricle leads to regular fluctuations in arterial blood flow and pressure (31, 36, 37). During LV systole, the pressure differential decreases and blood flow across the pump increases resulting in oscillations in arterial blood flow even as the aortic valve remains closed. The cyclical flow can produce pulse pressures in the range 5–25 mm Hg (38). A myopathic LV still follows the Frank-Starling principle and increases contractility in response to increased preload. The pulsatility index displayed on HMII models is the mathematical difference in maximal and minimal flows divided by the average flow per cardiac cycle (15). Normal ranges are 3.5–5.5. It should be noted that this calculated value is not reliable (12). In HW models, the pulsatility is not mathematically calculated, but flow and power pulsatility can be visualized graphically on the display. Practically, flow pulsatility represents the equilibrium between native cardiac function and LV preload with ventricular unloading by the LVAD (15, 19, 28). During a change in clinical status, it can aid in diagnosis. Increased pump speed will decrease pulsatility index. For a fixed speed, a drop in pulsatility index suggests either decreased LV preload or contractility.
INITIAL POSTOPERATIVE MANAGEMENT AND HEMODYNAMICS
Because pulse usually cannot be palpated, measurement of blood pressure is often difficult. Thus, in the immediate postoperative period, blood pressure is best measured by invasive arterial catheter. Automated cuff or manual auscultation does not yield a measurable value reliably, and values obtained usually underestimate mean arterial pressure (MAP) and systolic pressures (35, 39, 40). Occlusion pressures obtained by Doppler at the brachial artery correlate well with invasive arterial measurement. This measurement reflects MAP but not systolic pressure (39). In general, MAP is maintained at approximately 70–90 mm Hg (19). Assuming there is sufficient intracavitary volume, up titration of pump speed increases MAP and diastolic pressure without change in systolic pressure (40, 41). Excessive blood pressure can lead to neurologic events, bleeding, and reduced flow of LVAD.
Pulse oximetry can be unreliable in setting of little or no pulse. Low values require confirmation by arterial blood gas analysis (14).
Invasive monitoring with a pulmonary artery catheter is helpful to diagnose shock states and device function (13, 42). Echocardiography provides other valuable information to determine preload, ventricular function, and device position and performance (43) (Fig. 6). Septal positioning and chamber size provide assessment of cardiac function and guide pump speed adjustments. Assessment of aortic valve opening is important to appreciate the contribution of native cardiac function to overall output and valvular function (44).
In the immediate postoperative period, hemodynamic management is based on determination of MAP, cardiac index, and ventricular function. A combination of inotropes, vasodilators, and vasopressors are used in addition to augmentation of intravascular volume and speed adjustments. See Table 1 for treatment recommendations in the early postoperative period.
The approach to hypotension is described in Figure 7. Vasodilation leads to an increase in flows (assuming adequate preload) and can be an early sign of sepsis. Hypotension with low LVAD flows requires assessment of cardiac function and filling pressures, as this can be a sign of hypovolemia, RV failure, arrhythmias, or other causes, such as tamponade or device-related complications.
RV FAILURE AND PULMONARY HYPERTENSION
After implantation, RV geometry changes as the septum shifts to the left with LV unloading, causing an increase in RV compliance but a decrease in contractility. Venous return is increased due to improved cardiac output from the LVAD, but right ventricular afterload remains high due to pulmonary hypertension from chronic heart failure. Although difficult to predict, acute RV failure develops in some patients after LVAD implantation (45–47). This is characterized by elevated central venous pressures, elevated pulmonary vascular resistance, and pulmonary artery pressures with reduced LVAD flows and cardiac output (13). In very severe RV failure, pulmonary artery pressures may be low or normal. In as little as 1 month after implantation, right- and left-sided filling pressures decrease, and the right ventricular stroke work index decreases whereas cardiac output increases (11, 47). The improvement in pulmonary hemodynamics is sustained throughout the duration of LVAD support and persists after heart transplant as well (11, 48).
Milrinone reduces pulmonary artery pressures and pulmonary vascular resistance (PVR) without inducing excessive hypotension or arrhythmias (15, 49) (Fig. 6). Selective pulmonary vasodilators, such as inhaled nitric oxide or epoprostenol, can also be used. Because RV contractility is impaired by systemic hypotension (50), MAP should be maintained between 70 and 90 mm Hg (51, 52). Phosphodiesterase 5a inhibitors such as sildenafil are used to decrease pulmonary vascular resistance (53). Those failing drug therapy should be considered for temporary RV assist device placement, venoarterial extracorporeal membrane oxygenation (54), or total artificial heart. Some centers have implanted the HW ventricular assist device (VAD) in both the RV and LV for biventricular support (55).
RESPIRATORY FAILURE AND MECHANICAL VENTILATION
Pulmonary vasoconstriction in regions of underventilated alveoli may elevate PVR and worsen RV dysfunction (56). The impact of mechanical ventilation on LVAD performance or cardiac output has not been studied in vivo, and optimal ventilator settings for LVAD patients are uncertain. Computer models of continuous-flow pumps have demonstrated a decrease in LV efficiency and an increase in RV efficiency with increasing positive intrathoracic pressure. This offsets the increase in RV stroke work created by the continuous-flow pump (57). Therefore, patients may experience worsening of RV failure after extubation. The consequence of airway pressure and the interplay of ventilation and perfusion to RV performance should be considered when managing LVAD patients with respiratory failure.
Patients with LVADs are frequently readmitted with complications (58), most frequently in the first 6 months. Complications include bleeding, heart failure, neurologic events, arrhythmia, infection, and thrombosis or hemolysis (7, 58,59).
Management of LVAD patients requires balancing the risks of thrombosis and hemorrhage. Both procoagulant and anticoagulant pathways are activated in patients on LVAD support (60). Contact activation of platelets may not be as great as once thought, and in fact, platelet activity may be significantly impaired, independent of aspirin use (61–63). Large von Willebrand factor monomers are absent, characteristic of acquired type 2 von Willebrand syndrome due to shear stress from the rotor, but return to normal after device explantation (61).
Anticoagulation protocols vary by institution, device (62), and individual patient. Anticoagulation with both antiplatelet agent and warfarin is the norm. However, recent data suggest that hemorrhagic complications far outweigh thrombotic complications (64–66). Furthermore, anticoagulation in the early postoperative period may not be necessary (65). Warfarin is begun after drains are removed, usually on the third postoperative day. The target international normalized ratio (INR) in outpatients ranges from 1.5 to 2.5 (64, 67). Aspirin is often given in doses from 50 to 325 mg. Some institutions dose patients based on tests of platelet function (evidence of acquired von Willebrand syndrome) (61), clinical condition (63), or specific device protocols.
Major thrombotic events in LVAD patients include pump thrombosis and arterial thromboembolism. Thrombi form on the impeller or areas of low flow, such as the aortic valve, atrial appendage, or a dilated LV. Ischemic strokes occur in about 8–10% of LVAD patients (7, 59). Active infection increases risk of stroke, because of increased procoagulant pathway activity (68, 69). Hemolysis is present in about 4% of patients with pulsatile or continuous-flow LVAD (7, 59).
Signs of pump thrombosis include hemolysis, thromboembolism, heart failure, and end-organ hypoperfusion with elevated power and flow readings on LVAD (71) (Fig. 6; Table 1). Pump thrombosis has been managed with thrombolysis (72), heparin (67), or lepirudin (61). Patients failing medical therapy or requiring emergent treatment are offered device exchange (71, 73) or urgent transplantation (61).
Bleeding is the most frequent adverse event (74). Early bleeding requiring surgery is seen in 26% of patients (70). The most common sites of early bleeding are mediastinal, followed by thoracic pleural space, lower gastrointestinal (GI) tract, chest wall, and upper GI tract (75). Patients who are in consideration for transplantation should receive only leukoreduced, irradiated blood products.
Common bleeding events more than 30 days after implant are epistaxis, GI bleeding, mediastinal and thoracic bleeding, and intracranial hemorrhage (reviewed in ) (7, 70, 76). Average INR is not higher in GI bleeding patients than in nonbleeding patients (77). Causes of GI bleeding include most commonly arteriovenous malformations in addition to bleeding from polyps, gastric feeding tubes, and mucosal erosions from gastroesophageal reflux.
Intracerebral hemorrhage can occur as a result of hemorrhagic conversion of ischemic strokes, traumatic subdural and subarachnoid hemorrhage, and spontaneous intracranial hemorrhage. Intracranial hemorrhage is a common neurologic complication in LVADs. Many patients are not excessively anticoagulated at the time of their hemorrhage (78, 79), and postoperative INR or anticoagulation regimen were not associated with neurologic complications (80). We and others have observed excessively high LVAD flows and hypertension (MAP > 90 mmHg) to predispose patients to spontaneous intracranial hemorrhage. Intraparenchymal hemorrhage carries an especially poor prognosis, with a 30-day mortality rate of 59% (78).
An approach to GI bleeding by many programs (Fig. 8) includes holding anticoagulation temporarily. If bleeding stops, goal INR can be slowly increased while continuing to withhold aspirin. Patients have managed without anticoagulation for more than a year without thrombotic complications (62,67, 81, 82). After an intracerebral hemorrhage event, retrospective analysis indicates that aspirin can be resumed after 1 week and warfarin after 10 days without expansion of the hemorrhage or thrombotic events (77).
In patients with nonsurgical life-threatening hemorrhage unresponsive to standard measures, recombinant activated factor VIIa can be used. Dramatically higher thromboembolic events have been experienced with higher doses of recombinant factor VIIa (84).
Infection is the second most common cause of death after cardiac failure (84). The International Society of Heart and Lung Transplantation (ISHLT) classifies infectious complications based on their relationship to the device (51). However, infection of any kind is associated with increased hospital stay and increased mortality (85). Device-associated infections often occur after hospital discharge (86). In addition, an association has been noted between postoperative infections and neurologic complications (69, 79, 80).
LVAD-specific infections are driveline or pump pocket infections. These are characterized by localized warmth and erythema, cellulitis, fever, and leukocytosis. These infections can ascend into pump pocket or descend from the pump. Pump-pocket infection may also exhibit drainage from the driveline exit site and abdominal tenderness. CT, leukocyte-tagged planar scintigraphy, or hybrid single-photon emission-CT have limited utility in diagnosis (36, 86). Ultrasound can identify fluid collections and guide needle aspiration. Deep tissue swabs or biopsies from devices should be obtained where feasible and appropriate.
Most LVAD-specific infections are caused by Gram-positive organisms, Staphylococcus aureus most commonly, but Enterococcus and other Staphylococcus species are also frequently isolated. The Gram-negative pathogen most frequently isolated in LVAD-specific infections is Pseudomonas aeruginosa (87).
Infections of all types need aggressive treatment due to the risk of seeding the device. Localized infection of driveline or surgical site can be empirically treated with Gram-positive coverage alone, with coverage of resistant organisms as dictated by institutional prevalence and resistance profile as well as the patient’s history of infection and prior antimicrobial treatment. Deeper wound infections or pump pocket infections are often empirically treated with Gram-negative and Gram-positive coverage. Although the driveline itself cannot be replaced without replacing the pump as well, surgical revision to move the driveline away from an infected tract is sometimes performed. Deeper tissue infections are often treated with surgical debridement (88), and pump pocket infections are sometimes treated with antibiotic impregnated beads (89), omental or muscle flap, or vacuum-assisted closure devices (90–92). In severe or refractory cases, the device is explanted and patients are subsequently transplanted (85) or given extracorporeal support until transplant can occur.
There have not been any trials addressing the need for secondary prophylaxis prior to surgical/dental procedures. The ISHLT guidelines suggest that secondary prophylaxis would be appropriate, but it remains at the discretion of the treating physician (51).
Although not necessary for LVAD function, loss of atrial kick can still lead to decompensation due to diminished RV cardiac output and function, and patients may therefore require rate or rhythm control. In the absence of a contraindication, the target INR is raised to 2–2.5.
Ventricular arrhythmias are common post-LVAD (93). Reentrant circuits can be created by placement of the LVAD cannula (6, 15). Arrhythmias can also be triggered by contact between the cannula and the ventricular septum during suction events caused by hypovolemia, RV failure, or small ventricular size. Cannula malposition can occur months after implantation due to migration of the device from significant changes in weight or scar tissue (94), and cause recurrent ventricular arrhythmias.
Ventricular arrhythmias are often treated in stepwise fashion. First, the LVAD speed is decreased to allow for increased ventricular filling, which may shift the cannula away from the septal wall. Hypovolemia is treated with fluid boluses. β-blockers and amiodarone are first-line antiarrhythmics, plus mexiletine in refractory ventricular tachycardia. Other antiarrhythmics (sotalol, lidocaine) can be used as needed. No change in INR target is indicated (94). In many cases, antiarrhythmic therapy can be titrated off over time since the prevalence is highest in the first month after implantation (94, 95). Those with refractory ventricular tachycardia may be eligible for catheter ablation, cannula repositioning, or device exchange.
The prevalence and severity of aortic insufficiency tends to increase with the duration of LVAD support (16). At high LVAD speeds, the native heart works in series with LVAD pump, and the aortic valve does not open. At lower speeds, the LV works in parallel with the LVAD, and LV contraction ejects blood across the aortic valve. However, maximum opening area and time are greatly reduced, resulting in a functional aortic stenosis. Higher transvalvular pressure and increased strain on valve leaflets leads to fusion or incompetence (5, 43) which can lead to regurgitation (95). Aortic regurgitation creates a continuous loop of oxygenated blood from the aorta to the LVAD that does not reach the systemic circulation, reducing the effectiveness of the pump, leading to pulmonary edema and increased shear stress on RBCs (5). When the aortic valve does not open normally, the patient is at risk for thrombosis on the aortic valve (18), posing a threat of embolism to the brain or other organs. Serial echocardiograms are used to determine aortic valve opening and make speed adjustments to balance optimal valve function with LV unloading.
Noncardiac surgery can be performed but presents significant risk of morbidity due to bleeding. A VAD coordinator or nurse familiar with the management of the device should accompany patients in the operating room to manage the console, monitor LVAD flow, and address any alarms. If emergency surgery at a center without VAD support is necessary, care providers should call the manufacturer or nearest hospital with a VAD program to obtain advice and recommendations on management of the device. General anesthesia can be administered safely. Arterial cannulation should be used to monitor MAP. Intra-abdominal procedures must proceed with extreme caution to avoid encountering the subcutaneously tunneled driveline. Ultrasound can be used to mark the driveline’s location. Electrocautery is safe with LVAD, but implanted defibrillators should be deactivated prior to surgery.
No protocols exist for managing anticoagulation in the perioperative period, and a variety of approaches have been used (96). Given the low long-term risk of minimal anticoagulation and high risk of perioperative bleeding in anticoagulated patients (64, 67), it seems prudent to discontinue warfarin 5 days prior to elective surgery (96). Antiplatelet therapy with low-dose aspirin can be continued, and patients with additional reasons for anticoagulation (atrial fibrillation, acute thromboembolism) may be bridged with IV unfractionated heparin (96).
DEVICE STOPPAGE AND CARDIAC ARREST
LVAD patients in cardiac arrest should be managed with the Advanced Cardiac Life Support (ACLS) algorithm for cardiac arrest with a few caveats. Patients with device stoppage can present in severe cardiogenic shock or full arrest and should be managed appropriately while searching for the cause of malfunction. Once restarted, a major concern is thromboembolism from the device. Device exchange can be performed emergently if necessary and feasible. Pulses are not a reliable metric for resuscitation. Electrical activity without cardiac contractility should prompt a search for underlying causes, such as tension pneumothorax and electrolyte derangements. In case of cardiac arrest not due to device malfunction, patients may or may not have adequate flow through their device. When patients in terminal rhythms have power outputs indicating flow through the device, a “chemical code” using only electrical cardioversion/defibrillation, epinephrine, and atropine according to ACLS guidelines may be sufficient to terminate the arrhythmia and restart the heart. When power output is extremely low, chest compressions may be necessary to maintain perfusion. The major risk factor to chest compressions during cardiopulmonary resuscitation is dislodgement of the device or its outflow cannula, located directly beneath the sternum. This is mainly of concern with the larger preperitoneal devices, such as HMII. A potential alternative is abdominal compressions, given 1–2 inches left of midline. Abdominal compressions in an LVAD patient maintained a coronary perfusion pressure of 15 mm Hg (97), the minimum required to achieve return of spontaneous circulation and better than the perfusion pressure usually achieved with chest compressions (98). At return of spontaneous circulation, care should be taken to support the ischemic RV.
END OF LIFE
Stopping the device at the request of a patient or surrogate is not considered physician-assisted death but rather allowing natural death to occur (30). This may be due to a process unrelated to the device that will inevitably lead to the patient’s demise despite LVAD support. More complex still is the patient who has experienced complications and thus suffers from a new set of comorbidities, the burdens of which exceed the benefits of living with LVAD support (99). In this situation, the patient or surrogate may request the device be turned off in compliance with the patient’s advanced directives. Unfortunately, most patients’ advance directives do not mention the LVAD or withdrawal of LVAD support (100). Device deactivation results in death of the patient, usually within minutes (37).
As the demand for advanced heart failure treatment continues to grow and technology improves, intensivists are increasingly likely to encounter patients supported with LVADs either during their initial hospitalization or on subsequent admissions for complications. Management of these unique patients in the ICU is best accomplished with a multidisciplinary team that includes specialists in advanced heart failure, LVAD nurse coordinators, and intensivists.
We thank Dr. Samer Najjar for his thoughtful review of this manuscript.
1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: A report from the American Heart Association. Circulation. 2012; 125:e2–e220
2. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004; 292:344–350
3. Costanzo MR, Mills RM, Wynne J:. Characteristics of “Stage D” heart failure: Insights from the Acute Decompensated Heart Failure National Registry Longitudinal Module (ADHERE LM). Am Heart J. 2008; 155:339–347
4. Taylor DO, Stehlik J, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: Twenty-sixth official adult heart transplant report-2009. J Heart Lung Transplant. 2009; 28:1007–1022
5. Miller LW, Pagani FD, Russell SD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007; 357:885–896
6. Rogers JG, Aaronson KD, Boyle AJ, et al. Continuous flow left ventricular assist device improves functional capacity and quality of life of advanced heart failure patients. J Am Coll Cardiol. 2010; 55:1826–1834
7. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009; 361:2241–2251
8. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): On track to compete with heart transplantation? J Thorac Cardiovasc Surg. 2012; 144:584–603
9. Williams ML, Trivedi JR, McCants KC, et al. Heart transplant vs left ventricular assist device in heart transplant-eligible patients. Ann Thorac Surg. 2011; 91:1330–1333; discussion 1333–1334
10. Kirklin JK, Naftel DC, Kormos RL, et al. The Fourth INTERMACS Annual Report: 4,000 implants and counting. J Heart Lung Transplant. 2012; 31:117–126
11. Frazier OH:. Current status of cardiac transplantation and left ventricular assist devices. Tex Heart Inst J. 2010; 37:319–321
12. Lund LH, Gabrielsen A, Tiren L, et al. Derived and displayed power consumption, flow, and pulsatility over a range of HeartMate II left ventricular assist device settings. ASAIO J. 2012; 58:183–190
13. Butler KC, Dow JJ, Litwak P, et al. Development of the Nimbus/University of Pittsburgh innovative ventricular assist system. Ann Thorac Surg. 1999; 68:790–794
14. Christensen DM:. Physiology of continuous-flow pumps. AACN Adv Crit Care. 2012; 23:46–54
15. Griffith BP, Kormos RL, Borovetz HS, et al. HeartMate II left ventricular assist system: From concept to first clinical use. Ann Thorac Surg. 2001; 71:S116–S120; discussion S114–S116
16. DeBakey ME, Teitel ER:. Use of the MicroMed DeBakey VAD for the treatment of end-stage heart failure. Expert Rev Med Devices. 2005; 2:137–140
17. John R. Current axial-flow devices—the HeartMate II and Jarvik 2000 left ventricular assist devices. Semin Thorac Cardiovasc Surg. 2008; 20:264–272
18. Timms D. A review of clinical ventricular assist devices. Med Eng Phys. 2011; 33:1041–1047
19. Wilson SR, Givertz MM, Stewart GC, et al. Ventricular assist devices the challenges of outpatient management. J Am Coll Cardiol. 2009; 54:1647–1659
20. Larose JA, Tamez D, Ashenuga M, et al. Design concepts and principle of operation of the HeartWare ventricular assist system. ASAIO J. 2010; 56:285–289
21. Ozbaran M, Yagdi T, Engin C, et al. New circulatory support system: Heartware. Transplant Proc. 2012; 44:1726–1728
22. Tuzun E, Roberts K, Cohn WE, et al. In vivo evaluation of the HeartWare centrifugal ventricular assist device. Tex Heart Inst J. 2007; 34:406–411
23. Anyanwu AC:. Technique for less invasive implantation of Heartmate II left ventricular assist device without median sternotomy. Semin Thorac Cardiovasc Surg. 2011; 23:241–244
24. Popov AF, Hosseini MT, Zych B, et al. HeartWare left ventricular assist device implantation through bilateral anterior thoracotomy. Ann Thorac Surg. 2012; 93:674–676
25. Tsiouris A, Brewer RJ, Borgi J, et al. Is resternotomy a risk for continuous-flow left ventricular assist device outcomes? J Card Surg. 2013; 28:82–87
26. Takayama H, Yang JA, Naka Y. Tips on tuning each device: Technical pearls. Cardiol Clin. 2011; 29:551–556
28. Thoratec Corporation Thoratec Corporation Heartmate II LVAS Operating Manual. 2010; Pleasanton, CA Thoratec Corporation
29. Kikugawa D:. Motor current waveforms as an index for evaluation of native cardiac function during left ventricular support with a centrifugal blood pump. Artif Organs. 2001; 25:703–708
30. Brassard P, Jensen AS, Nordsborg N, et al. Central and peripheral blood flow during exercise with a continuous-flow left ventricular assist device: Constant versus increasing pump speed: A pilot study. Circ Heart Fail. 2011; 4:554–560
31. Salamonsen RF, Mason DG, Ayre PJ:. Response of rotary blood pumps to changes in preload and afterload at a fixed speed setting are unphysiological when compared with the natural heart. Artif Organs. 2011; 35:E47–E53
32. Andersen M, Gustafsson F, Madsen PL, et al. Hemodynamic stress echocardiography in patients supported with a continuous-flow left ventricular assist device. JACC Cardiovasc Imaging. 2010; 3:854–859
33. Jacquet L, Vancaenegem O, Pasquet A, et al. Exercise capacity in patients supported with rotary blood pumps is improved by a spontaneous increase of pump flow at constant pump speed and by a rise in native cardiac output. Artif Organs. 2011; 35:682–690
34. Estep JD, Stainback RF, Little SH, et al. The role of echocardiography and other imaging modalities in patients with left ventricular assist devices. JACC Cardiovasc Imaging. 2010; 3:1049–1064
35. Karantonis DM, Lovell NH, Ayre PJ, et al. Identification and classification of physiologically significant pumping states in an implantable rotary blood pump. Artif Organs. 2006; 30:671–679
36. Jakovljevic DG, George RS, Nunan D, et al. The impact of acute reduction of continuous-flow left ventricular assist device support on cardiac and exercise performance. Heart. 2010; 96:1390–1395
37. Martina JR, Westerhof BE, Van Goudoever J, et al. Noninvasive blood pressure measurement by the Nexfin monitor during reduced arterial pulsatility: A feasibility study. ASAIO J. 2010; 56:221–227
38. Potapov EV, Loebe M, Nasseri BA, et al. Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device. Circulation. 2000; 102:III183––III187
39. Bennett MK, Roberts CA, Dordunoo D, et al. Ideal methodology to assess systemic blood pressure in patients with continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2010; 29:593–594
40. Myers TJ, Bolmers M, Gregoric ID, et al. Assessment of arterial blood pressure during support with an axial flow left ventricular assist device. J Heart Lung Transplant. 2009; 28:423–427
41. Hayward CS, Salamonsen R, Keogh AM, et al. Effect of alteration in pump speed on pump output and left ventricular filling with continuous-flow left ventricular assist device. ASAIO J. 2011; 57:495–500
42. Anderson CA, Filsoufi F, Aklog L, et al. Liberal use of delayed sternal closure for postcardiotomy hemodynamic instability. Ann Thorac Surg. 2002; 73:1484–1488
43. May-Newman K, Enriquez-Almaguer L, Posuwattanakul P, et al. Biomechanics of the aortic valve in the continuous flow VAD-assisted heart. ASAIO J. 2010; 56:301–308
44. Rasalingam R, Johnson SN, Bilhorn KR, et al. Transthoracic echocardiographic assessment of continuous-flow left ventricular assist devices. J Am Soc Echocardiogr. 2011; 24:135–148
45. Aaronson KD, Slaughter MS, Miller LW, et al. Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation. Circulation. 2012; 125:3191–3200
46. Kormos RL, Teuteberg JJ, Pagani FD, et al. Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: Incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg. 2010; 139:1316–1324
47. Lee S, Kamdar F, Madlon-Kay R, et al. Effects of the HeartMate II continuous-flow left ventricular assist device on right ventricular function. J Heart Lung Transplant. 2010; 29:209–215
48. John R, Liao K, Kamdar F, et al. Effects on pre- and posttransplant pulmonary hemodynamics in patients with continuous-flow left ventricular assist devices. J Thorac Cardiovasc Surg. 2010; 140:447–452
49. Kihara S, Kawai A, Fukuda T, et al. Effects of milrinone for right ventricular failure after left ventricular assist device implantation. Heart Vessels. 2002; 16:69–71
50. Green EM, Givertz MM:. Management of acute right ventricular failure in the intensive care unit. Curr Heart Fail Rep. 2012; 9:228–235
51. Feldman D, Pamboukian SV, Teuteberg JJ, et al. International Society for Heart and Lung Transplantation The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summay. J Heart Lung Transplant. 2013; 32:157–187
52. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant. 2010; 29:S1––39
53. Tedford RJ, Hemnes AR, Russell SD, et al. PDE5A inhibitor treatment of persistent pulmonary hypertension after mechanical circulatory support. Circ Heart Fail. 2008; 1:213–219
54. Scherer M, Sirat AS, Moritz A, et al. Extracorporeal membrane oxygenation as perioperative right ventricular support in patients with biventricular failure undergoing left ventricular assist device implantation. Eur J Cardiothorac Surg. 2011; 39:939–944
55. Strueber M, Meyer AL, Malehsa D, et al. Successful use of the HeartWare HVAD rotary blood pump for biventricular support. J Thorac Cardiovasc Surg. 2010; 140:936–937
56. Balanos GM, Talbot NP, Dorrington KL, et al. Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography. J Appl Physiol. 2003; 94:1543–1551
57. De Lazzari C, Darowski M, Ferrari G, et al. The impact of rotary blood pump in conjunction with mechanical ventilation on ventricular energetic parameters—Numerical simulation. Methods Inf Med. 2006; 45:574–583
58. Hasin T, Marmor Y, Kremers W, et al. Readmissions after implantation of axial flow left ventricular assist device. J Am Coll Cardiol. 2013; 61:153–163
59. Yuan N, Arnaoutakis GJ, George TJ, et al. The spectrum of complications following left ventricular assist device placement. J Cardiac Surg. 2012; 27:63–638
60. John R, Panch S, Hrabe J, et al. Activation of endothelial and coagulation systems in left ventricular assist device recipients. Ann Thorac Surg. 2009; 88:1171–1179
61. Meyer AL, Malehsa D, Bara C, et al. Acquired von Willebrand syndrome in patients with an axial flow left ventricular assist device. Circ Heart Fail. 2010; 3:675–681
62. Rossi M, Serraino GF, Jiritano F, et al. What is the optimal anticoagulation in patients with a left ventricular assist device? Interact Cardiovasc Thorac Surg. 2012; 15:733–740
63. Slaughter MS, Sobieski MA 2nd, Graham JD, et al. Platelet activation in heart failure patients supported by the HeartMate II ventricular assist device. Int J Artif Organs. 2011; 34:461–468
64. Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: Analysis of outpatient anti-coagulation. J Heart Lung Transplant. 2009; 28:881–887
65. Slaughter MS, Naka Y, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant. 2010; 29:616–624
66. Suarez J, Patel CB, Felker GM, et al. Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices. Circ Heart Fail. 2011; 4:779–784
67. John R, Kamdar F, Liao K, et al. Low thromboembolic risk for patients with the Heartmate II left ventricular assist device. J Thorac Cardiovasc Surg. 2008; 136:1318–1323
68. Kato TS, Ota T, Schulze PC, et al. Asymmetric pattern of cerebrovascular lesions in patients after left ventricular assist device implantation. Stroke. 2012; 43:872–874
69. Nakajima I, Kato TS, Komamura K, et al. Pre- and post-operative risk factors associated with cerebrovascular accidents in patients supported by left ventricular assist device. Circ J. 2011; 75:1138–1146
70. Pagani FD, Miller LW, Russell SD, et al. Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device. J Am Coll Cardiol. 2009; 54:312–321
71. Aissaoui N, Borgermann J, Gummert J, et al. HeartWare continuous-flow ventricular assist device thrombosis: The bad Oeynhausen experience. J Thorac Cardiovasc Surg. 2012; 143:e37–e39
72. Rothenburger M, Wilhelm MJ, Hammel D, et al. Treatment of thrombus formation associated with the MicroMed DeBakey VAD using recombinant tissue plasminogen activator. Circulation. 2002; 106:I189–I192
73. Tang GH, Kim MC, Pinney SP, et al. Failed repeated thrombolysis requiring left ventricular assist device pump exchange. Catheter Cardiovas Interv. 2013; 81:1072–1074
74. Slaughter MS:. Hematologic effects of continuous flow left ventricular assist devices. J Cardiov Transl Res. 2010; 3:618–624
75. Jessup M, Goldstein D, Ascheim DD, et al. Risk for bleeding after MSCD implant: An analysis of 2358 patients in INTERMACS. J Heart Lung Transplant. 2011; 30:(Suppl I)S9
76. Genovese EA, Dew MA, Teuteberg JJ, et al. Incidence and patterns of adverse event onset during the first 60 days after ventricular assist device implantation. Ann Thorac Surg. 2009; 88:1162–1170
77. Crow S, John R, Boyle A, et al. Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices. J Thorac Cardiovasc Surg. 2009; 137:208–215
78. Wilson TJ, Stetler WR Jr, Al-Holou WN, et al. Management of intracranial hemorrhage in patients with left ventricular assist devices. J Neurosurg. 2013; 118:1063–1068
79. Tsukui H, Abla A, Teuteberg JJ, et al. Cerebrovascular accidents in patients with a ventricular assist device. J Thorac Cardiovasc Surg. 2007; 134:114–123
80. Kato TS, Schulze PC, Yang J, et al. Pre-operative and post-operative risk factors associated with neurologic complications in patients with advanced heart failure supported by a left ventricular assist device. J Heart Lung Transplant. 2012; 31:1–8
81. Pereira NL, Chen D, Kushwaha SS, et al. Discontinuation of antithrombotic therapy for a year or more in patients with continuous-flow left ventricular assist devices. Interact Cardiovasc Thorac Surg. 2010; 11:503–505
82. Saito S, Westaby S, Piggott D, et al. Reliable long-term non-pulsatile circulatory support without anticoagulation. Eur J Cardiothorac Surg. 2001; 19:678–683
83. Bruckner BA, DiBardino DJ, Ning Q, et al. High incidence of thromboembolic events in left ventricular assist device patients treated with recombinant activated factor VII. J Heart Lung Transplant. 2009; 28:785–790
84. Kirklin JK, Naftel DC, Kormos RL, et al. Second INTERMACS annual report: More than 1,000 primary left ventricular assist device implants. J Heart Lung Transplant. 2010; 29:1–10
85. Topkara VK, Kondareddy S, Malik F, et al. Infectious complications in patients with left ventricular assist device: Etiology and outcomes in the continuous-flow era. Ann Thorac Surg. 2010; 90:1270–1277
86. Litzler PY, Manrique A, Etienne M, et al. Leukocyte SPECT/CT for detecting infection of left-ventricular-assist devices: Preliminary results. J Nucl Med. 2010; 51:1044–1048
87. Acharya MN, Som R, Tsui S:. What is the optimum antibiotic prophylaxis in patients undergoing implantation of a left ventricular assist device? Interact Cardiovasc Thorac Surg. 2012; 14:209–214
88. Chamogeorgakis T, Koval CE, Smedira NG, et al. Outcomes associated with surgical management of infections related to the HeartMate II left ventricular assist device: Implications for destination therapy patients. J Heart Lung Transplant. 2012; 31:904–906
89. Holman WL, Rayburn BK, McGiffin DC, et al. Infection in Ventricular assist devices: Prevention and treatment. Ann Thorac Surg. 2003; 75:S48–S57
90. Shafii AE, Chamogeorgakis TP, Gonzalez-Stawinski G. Omental flap transposition with intra-abdominal relocation for LVAD pump-pocket infection. J Heart Lung Transplant. 2011; 30:1421–1422
91. Baradarian S, Stahovich M, Krause S, et al. Case series: clinical management of persistent mechanical assist device driveline drainage using vacuum-assisted closure therapy. ASAIO J. 2006; 52:354–356
92. Garatt i A, Giuseppe B, Russo CF, et al. Drive-line exit-site infection in a patient with axial-flow pump support: Successful management using vacuum-assisted therapy. J Heart Lung Transplant. 2007; 26:956–959
93. Andersen M, Videbaek R, Boesgaard S, et al. Incidence of ventricular arrhythmias in patients on long-term support with a continuous-flow assist device (HeartMate II). J Heart Lung Transplant. 2009; 28:733–735
94. Boyle A. Arrhythmias in patients with ventricular assist devices. Curr Opin Cardiol. 2012; 27:13–18
95. Tuzun E, Rutten M, Dat M, et al. Continuous-flow cardiac assistance: Effects on aortic valve function in a mock loop. J Surg Res. 2011; 171:443–447
96. Morgan JA, Paone G, Nemeh HW, et al. Non-cardiac surgery in patients on long-term left ventricular assist device support. J Heart Lung Transplant. 2012; 31:757–763
97. Rottenberg EM, Heard J, Hamlin R, et al. Abdominal only CPR during cardiac arrest for a patient with an LVAD during resternotomy: A case report. J Cardiothorac Surg. 2011; 6:91
98. Paradis NA, Martin GB, Rivers EP, et al. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA. 1990; 263:1106–1113
99. Swetz KM, Ottenberg AL, Freeman MR, et al. Palliative care and end-of-life issues in patients treated with left ventricular assist devices as destination therapy. Curr Heart Fail Rep. 2011; 8:212–218
100. Swetz KM, Mueller PS, Ottenberg AL, et al. The use of advance directives among patients with left ventricular assist devices. Hosp Pract (1995). 2011; 39:78–84
Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins