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Durable Mechanical Circulatory Support in Advanced Heart Failure

A Critical Care Cardiology Perspective

      Keywords

      Key points

      • Heart transplantation is often unavailable for most patients with advanced heart failure because of a limited donor supply, so mechanical circulatory support (MCS) is slowly becoming established as a primary standard.
      • Selecting appropriate patients for MCS involves meeting a multitude of prespecifications, as one would for transplant evaluation.
      • As technology evolves to bring forth more durable, smaller devices, the selection criteria for appropriate recipients of MCS will expand to encompass a broader, less sick population.
      • The “Holy Grail” for MCS will be a focus on clinical recovery and explantation of devices rather than the current more narrowly defined indications of device therapy for life or as bridge to transplant.

      Scope

      Heart failure is responsible for more than 1 million hospitalizations annually in the United States, and its estimated costs amount to more than $38 billion.
      • Lindenfeld J.
      • Albert N.M.
      • Boehmer J.P.
      • et al.
      HFSA 2010 comprehensive heart failure practice guideline.
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      • et al.
      Heart disease and stroke statistics—2013 update: a report from the American Heart Association.
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      • Trogdon J.G.
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      • et al.
      Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.
      Though most patients are hospitalized with acute decompensated heart failure (ADHF) caused by worsening of chronic heart failure, 15% to 20% of ADHF hospitalizations represent new diagnoses of heart failure.
      • Joseph S.M.
      • Cedars A.M.
      • Ewald G.A.
      • et al.
      Acute decompensated heart failure: contemporary medical management.
      The latter often present with pulmonary edema and/or cardiogenic shock, and require cardiac intensive care unit (CICU) care.
      • O'Connor C.M.
      • Stough W.G.
      • Gallup D.S.
      • et al.
      Demographics, clinical characteristics, and outcomes of patients hospitalized for decompensated heart failure: observations from the impact-hf registry.
      Of the 80% of patients with chronic heart failure exacerbations, approximately 10% have advanced heart failure.
      • Joseph S.M.
      • Cedars A.M.
      • Ewald G.A.
      • et al.
      Acute decompensated heart failure: contemporary medical management.
      Patients with advanced heart failure are those with clinically significant circulatory compromise who require consideration of heart transplantation, mechanical circulatory support (MCS), continuous intravenous inotropic therapy, or hospice.
      • Peura J.L.
      • Colvin-Adams M.
      • Francis G.S.
      • et al.
      Recommendations for the use of mechanical circulatory support: device strategies and patient selection: a scientific statement from the American Heart Association.
      Heart transplantation is often unavailable for most patients with advanced heart failure because of a limited donor supply; therefore, MCS is slowly becoming established as a primary standard. The development of smaller, more durable left ventricular assist devices (LVADs) provides a practical and effective form of therapy as a bridge to transplantation (BTT), bridge to candidacy, and destination therapy (DT) for those otherwise not eligible for transplantation. These distinctions are becoming arbitrary however, and may be more appropriately supplanted by the concept of lifetime therapy, with consideration of transplantation when durable device therapy fails.

      Evolution of the coronary care unit

      With the advent of continuous electrocardiographic monitoring, the first coronary care units (CCU) were formed to decrease postmyocardial infarction arrhythmias and mortality in the 1960s.
      • Morrow D.A.
      • Fang J.C.
      • Fintel D.J.
      • et al.
      Evolution of critical care cardiology: transformation of the cardiovascular intensive care unit and the emerging need for new medical staffing and training models: a scientific statement from the American Heart Association.
      The institution of CCUs across the globe has swiftly decreased mortality from postmyocardial infarction. A paradigm shift is taking place, however, rendering the term “coronary care unit” no longer relevant because of the dramatically different and varied patient population such units now serve. The modern cardiac intensive care unit (CICU) manages patients with invasive and noninvasive hemodynamic monitoring, mechanical ventilation, renal replacement therapies, therapeutic hypothermia protocols, sepsis, pulmonary hypertension, inotropic support, advanced structural heart disease, and MCS. Cardiac intensivists thus require a working knowledge of the types of MCS devices available and associated complications they are likely to encounter.

      Clinical profiles and device selection

      The approach to MCS depends on patients’ clinical status and the trajectory of their heart failure syndrome. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) provides a clinical profile categorization of patients with heart failure according to clinical severity and acuity (Table 1).
      • Stevenson L.W.
      • Pagani F.D.
      • Young J.B.
      • et al.
      INTERMACS profiles of advanced heart failure: the current picture.
      Although most mechanical support therapy was initially developed for acute profiles 1 and 2, long-term durable devices are increasingly being implanted in patients with profiles 3 and 4.
      Table 1INTERMACS profiles
      Adapted from Stevenson LW, Pagani FD, Young JB, et al. INTERMACS profiles of advanced heart failure: the current picture. J Heart Lung Transplant 2009;28:535–41; with permission.
      INTERMACS ProfileProfile DescriptionTime Frame for Intervention
      Profile 1: Critical cardiogenic shockPatients with life-threatening hypotension despite rapidly escalating inotropic support “crash and burn”Within hours
      Profile 2: Progressive declinePatients with declining function despite intravenous inotropic support

      “Sliding on inotropes.” Also describes declining patients unable to tolerate inotropes
      Within a few days
      Profile 3: Stable but inotrope dependentStable on inotropic or temporary circulatory support, with demonstrated failure to wean “dependent stability”Weeks to a few months
      Profile 4: Resting symptomsStabilized but experiences daily symptoms of congestion at rest or during activities of daily living. Recurrent advanced heart failureWeeks to a few months
      Profile 5: Exertion intolerantComfortable at rest but symptomatic with any exertion. Exertion intolerantVariable urgency: depends on maintenance of nutrition, organ function, and activity
      Profile 6: Exertion limitedNo fluid overload at rest, but symptomatic within few minutes of exertion. Exertion limited or “walking wounded”Variable: depends on maintenance of nutrition, organ function, and activity level
      Profile 7: Advanced NYHA IIILiving comfortably with limited meaningful activityTransplantation or circulatory support may not currently be indicated
      Abbreviation: NYHA III, New York Heart Association functional class III.
      The contemporary CICU will be faced with the responsibility of caring for all profiles of these patients, not only for consideration of MCS device implantation but also for the management of their associated long-term complications. Short-term options such as the intra-aortic balloon pump, extracorporeal membrane oxygenation, surgically implanted extracorporeal MCS devices, and percutaneously implanted MCS devices play an important role in the management of those in cardiogenic shock and INTERMACS profile 1 (Table 2). A comprehensive approach to these short-term devices is covered elsewhere.
      Table 2Short-term MCS devices
      Adapted from Peura JL, Colvin-Adams M, Francis GS, et al. Recommendations for the use of mechanical circulatory sup-port: Device strategies and patient selection: a scientific statement from the American Heart Association. Circulation 2012;126:2650; with permission.
      DeviceCompanyMechanismSupportDuration
      IABPMultipleCounterpulsationLeft heart onlyDays
      ImpellaABIOMEDAxial flowLeft heart onlyDays
      TandemHeartCardiacAssistCentrifugalBiventricularDays
      ECMOMultipleCardiopulmonary bypassBiventricularDays to weeks
      BVS5000, AB5000ABIOMEDPulsatileRight, left, or biventricularWeeks
      Thoratec pVADThoratecPulsatileRight, left, or biventricularWeeks
      CentriMagLevitronixCentrifugalRight, left, or biventricularWeeks
      Abbreviations: ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump.

      Long-term circulatory support devices

      General Principles

      Long-term mechanical circulatory support devices have evolved from first-generation or pulsatile pumps to second-generation pumps with contact bearings/seals to now third-generation rotary pumps without mechanical contact bearings. The first-generation LVADs were large, positive displacement pumps with several moving parts. These devices were limited to patients with a body surface area of 1.5 m2 or more, did not require systemic anticoagulation, and were essentially the first MCS devices used in clinical practice. Prototypes include the Novacor LVAS, which was first implanted in 1984 as a BTT (WorldHeart, Salt Lake City, UT), and the HeartMate XVE (also called HeartMate I; Thoratec Corp, Pleasanton, CA). In the Thoratec PVAD (paracorporeal ventricular assist device) and Berlin Heart EXCOR (Berlin Heart AG, Berlin, Germany) systems, the blood pump lies external to the patient. The HeartMate XVE was the most widely used of these first-generation pumps, and mimicked normal human physiology in that following electrical activation of the ventricle, preload in the ventricle was ejected at each beat to the systemic circulation. Unfortunately, these pumps were limited by their large size and high rates of mechanical failure and infection, such that more than 50% of pumps needed to be replaced after 18 months of use.
      • Starling R.C.
      • Naka Y.
      • Boyle A.J.
      • et al.
      Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).
      Because of the aforementioned limitations, a new, second generation of LVADs emerged, which are axial pumps that use continuous rather than pulsatile blood flow. This technology enabled the development of pumps that have a single moving part, nearly one-fifth the size and weight of the first-generation pump. These devices draw blood from the left ventricle continuously via a drainage cannula inserted to the left ventricular apex with the use of a rotary pump, which propels blood to the systemic circulation in a nonphasic flow pattern to the ascending aorta. The speed of this rotary pump (8,000–10,000 rpm) can be adjusted directly to increase or decrease preload, thereby affecting blood pressure and output. Prototypes include the Jarvik 2000 (Jarvik Heart, New York, NY, USA), the MicroMed DeBakey VAD (MicroMed Technologies, Woodlands, TX, USA), and the HeartMate II, the most frequently used second-generation LVAD worldwide (Fig. 1). Aspirin in addition to systemic anticoagulation is used in all second-generation LVADs, and does not appear to lead to an increase in bleeding in comparison with first-generation pumps.
      • Slaughter M.S.
      • Rogers J.G.
      • Milano C.A.
      • et al.
      Advanced heart failure treated with continuous-flow left ventricular assist device.
      Figure thumbnail gr1
      Fig. 1(A) HeartMate XVE (first generation, pulsatile-flow pump) and HeartMate II (second generation, continuous-flow pump). (B) HeartMate II left ventricular assist device. (C) HeartMate II external equipment.
      (Courtesy of Thoratec, Pleasanton, CA.)
      Third-generation MCS devices are further miniaturized, and suitable for patients with a wide range of body surface areas. These devices also provide continuous blood flow generated by an axial or centrifugal rotor, and have a single moving part, which spins at rates between 2400 and 3200 rpm. The impeller is suspended within a pump-housing through a combination of passive magnets and hydrodynamic thrust bearings. There are no mechanical bearings or any points of contact between the impeller and its pump-housing (Fig. 2). The HeartWare or HVAD pump (HeartWare International, Inc, Framingham, MA), recently approved for BTT, is designed to be implanted in the pericardial space, obviating an abdominal pocket, and is thereby proposed to facilitate ease of implantation and shorten recovery times.
      • Wieselthaler G.M.
      • O Driscoll G.
      • Jansz P.
      • et al.
      Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial.
      Figure thumbnail gr2
      Fig. 2HeartWare device (third generation, centrifugal-flow pump).
      (Courtesy of HeartWare, Framingham, MA.)

      Clinical Trials

      The concept of long-term MCS originally emerged as an alternative to transplantation. However, owing to safety concerns and limited durability, the Food and Drug Administration (FDA) largely restricted device use to those patients eligible for cardiac transplantation, forging the concept of BTT. At present there are 8 devices approved by the FDA for long-term MCS as BTT (Table 3).
      • Peura J.L.
      • Colvin-Adams M.
      • Francis G.S.
      • et al.
      Recommendations for the use of mechanical circulatory support: device strategies and patient selection: a scientific statement from the American Heart Association.
      Of these, 3 are now approved for the indication of DT. The landmark trial that established DT as an accepted indication for MCS was the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial, published in 2001. This trial randomized 129 patients ineligible for transplant to medical therapy or MCS with the HeartMate XVE, and demonstrated a 27% absolute and 48% relative risk reduction.
      • Rose E.A.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Long-term use of a left ventricular assist device for end-stage heart failure.
      This investigation led to a follow-up trial, REMATCH II, which compared the pulsatile-flow HeartMate XVE (52% survival at 1 year) to the continuous-flow HeartMate II (68% survival at 1 year).
      • Slaughter M.S.
      • Rogers J.G.
      • Milano C.A.
      • et al.
      Advanced heart failure treated with continuous-flow left ventricular assist device.
      Compared with the dismal survival rate of 25% for patients medically managed in the 2 trials, the advent of LVADs has demonstrated the greatest magnitude of benefit in advanced heart failure relative to any therapy.
      Table 3Devices for long-term MCS approved by the US Food and Drug Administration
      Adapted from Peura JL, Colvin-Adams M, Francis GS, et al. Recommendations for the use of mechanical circulatory support: Device strategies and patient selection: a scientific statement from the American Heart Association. Circulation 2012;126:2653; with permission.
      DeviceCompanyMechanismSupportIndicationsPortable
      Thoratec pVADThoratecPulsatileRight, left, or biventricularBTT, BTRYes
      NovacorWorld HeartPulsatileLeftBTT, DTYes
      HeartMate XVEThoratecPulsatileLeftBTT, DTYes
      HeartMate IIThoratecAxial, continuousLeftBTT, DTYes
      Abiomed TAHABIOMEDPulsatileBiventricularBTT, DTYes
      CardioWest TAHSynCardiaPulsatileBiventricularBTTYes/No
      Berlin EXOR PediatricBerlinPulsatile/pneumaticRight, left, or biventricularBTTNo
      DeBakey childMicroMedContinuousLeftBTT, BTRNo
      Abbreviations: BTR, bridge to recovery; BTT, bridge to transplantation; DT, destination therapy.
      Most recently, patients with the HeartWare device were compared with those implanted contemporaneously with a HeartMate II device via INTERMACS registry data. The primary outcome was survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days. The primary outcome was achieved in 90.7% of the 140 patients who received the HeartWare pump and 90.1% of the 499 patients who received the HeartMate II, establishing prespecified grounds for noninferiority but not superiority.
      • Aaronson K.D.
      • Slaughter M.S.
      • Miller L.W.
      • et al.
      Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.
      The results of this trial led to FDA approval of the device in November 2012 for BTT. Although the rates of neurologic events are similar between the two groups, there is speculation that increased thrombotic events are seen with the HeartWare device.
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.
      The results of the Multi-Center Clinical Trial to Evaluate the HeartWare Ventricular Assist System (VAS) for Destination Therapy for Advanced Heart Failure (ENDURANCE), which compares the HeartMate II and HeartWare devices directly in patients who are not candidates for cardiac transplant are eagerly awaited.

      Troubleshooting and management

      Once discharged from hospital, long-term complications in patients with MCS involve device malfunction, arrhythmias, volume management, gastrointestinal (GI) bleeding, neurologic events, pump thrombosis, infection, and right heart failure. This section is intended to familiarize the cardiac intensivist with these commonly encountered issues and to suggest potential therapeutic approaches to management. Perioperative management of MCS devices is not discussed here, this being an aspect managed most commonly in surgical postoperative care units.

      Monitoring Device Function

      Because continuous-flow LVADs do not contain valves, in the presence of high afterload, low pump speeds, or turning the pump off, blood flow can become retrograde. LVADs also generate substantial negative pressure at the inflow cannula to unload the left ventricle, thereby creating the potential for septal shift or ventricular collapse if pump speeds are too high or patients are preload deplete. The HeartMate II console shows parameters of speed (set by the user and modifiable), power, pulsatility index (PI), and estimated flow, all of which are indicators of appropriate function (Figs. 3 and 4).
      • Slaughter M.S.
      • Pagani F.D.
      • Rogers J.G.
      • et al.
      Clinical management of continuous-flow left ventricular assist devices in advanced heart failure.
      Figure thumbnail gr3
      Fig. 3Sample Thoratec console display screen, showing Pump flow, Pump speed, Pulse index, and Pump power.
      Figure thumbnail gr4
      Fig. 4Device selection flow chart. BTC, bridge to candidacy; BTT, bridge to transplantation; DT, destination therapy; MCS, mechanical circulatory support; OHTx, orthotopic heart transplant.

      Power and flow

      At a given speed, power is a direct measure of the current and voltage applied to the motor. The flow is directly related to the power and pump speed. If power values are outside the anticipated physiologic range for a given speed, the flow will be displayed as “+ + +” or “− − −” to represent a calculated flow that is higher or lower than expected. Power also may be increased because of thrombus formation within the rotor, causing an erroneously high flow reading. The minimum flow reading is 3.0 L/min. Increases in volume status or decreases in afterload may cause increased flows. Conversely, an occlusion may decrease flow and correspondingly decrease power.

      Pulsatility index (PI)

      When the left ventricle contracts, it generates an increase in ventricular pressure and thereby causes an increase in pump flow. These flow increases are measured and averaged over a 15-second interval to produce the PI value displayed on the console. As the speed increases, the level of support from the device increases, causing less generation of increased pressure due to contraction, and therefore will correspond to a decreased PI. Decreased PI may also be observed in scenarios of decreased blood volume or preload depletion. Similarly, if there is an increase in contractility, as may be seen with increases in blood volume, inotropic medications, exercise, or intrinsic myocardial recovery, the PI will increase.

      Pump speed

      Optimal pump speed is achieved when cardiac index is sufficient (greater than 2.5 L/min/m2), often with the aid of visualizing the left ventricle via transthoracic echocardiography. Ideally the left ventricle is decompressed, but not so much so that it is collapsed or that the septum shifts toward the left. Over a period of time, excessive leftward septal shift leads to worsening right heart failure. Allowing for intermittent aortic valve opening and retaining some pulsatility is recommended.
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.
      The normal speed range is 8800 to 10,000 rpm for the HeartMate II and between 2400 and 3400 rpm for the HeartWare. Left ventricular dimensions, septal flattening, degree of aortic regurgitation (if any), mitral regurgitation, and aortic valve opening should be noted and taken into consideration when determining optimal pump speed for each individual patient.

      Hypertension and Hypotension

      Adequate unloading of the ventricle by the LVAD depends on afterload. Thus the control and maintenance of mean arterial blood pressure (MAP) at less than 90 mm Hg is important to allow for appropriate perfusion as well as to prevent retrograde flow. Specific antihypertensive agents have not been studied in the MCS population. It is generally accepted that one may use angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, hydralazine, nitrates, β-blockers, and dihydropyridine calcium-channel blockers for optimal control of blood pressure. Ideally, neurohormonally directed therapy is used to facilitate myocardial recovery over other agents.
      Hypotension in the LVAD patient must be evaluated carefully. The differential diagnosis is broad and includes dehydration, bleeding, right ventricular dysfunction, tamponade, improper cannula positioning, inadequate pump speed, infection, sepsis, and iatrogenic causes. Fig. 5 shows an algorithm on considerations of hypotension in the LVAD patient.
      Figure thumbnail gr5
      Fig. 5Evaluation of hypotension in a patient with a left ventricular assist device. JVP, jugular venous pressure; LV, left ventricle; MAP, mean arterial pressure; PAC, pulmonary artery catheter; RV, right ventricle; WBC, white blood cells.

      Arrhythmias

      LVAD patients are at risk for increased morbidity and mortality from atrial and ventricular arrhythmias, primarily because right ventricular filling and function are often compromised, leading to inadequate left ventricular filling, heart failure, syncope, and death. It is well known that the prevalence of atrial arrhythmias increases as symptoms of heart failure worsen in severity.
      • Maisel W.H.
      • Stevenson L.W.
      Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy.
      Because it is thought that left atrial distention from congestion and/or mitral regurgitation is the inciting cause, decompression of the left ventricle and, thereby, the left atrium with an LVAD may theoretically decrease this risk. Unfortunately this potential benefit is offset by an increased risk of perioperative atrial arrhythmias as seen in most cardiac surgery,
      • Zaman A.G.
      • Archbold R.A.
      • Helft G.
      • et al.
      Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification.
      and those with permanent atrial fibrillation are unlikely to have an altered substrate.
      • Boyle A.
      Arrhythmias in patients with ventricular assist devices.
      Thus the management of atrial arrhythmias is not much different than that for the general population. β-Blockers are used in preference to calcium-channel blockers for rate control, as is the case for all patients with heart failure. When poorly tolerated, a rhythm control strategy is favored, using either amiodarone or dofetilide in an attempt to restore sinus rhythm. Ablative therapy is generally reserved for refractory cases.
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.
      Most patients on LVAD support are on systemic anticoagulation; however, in those with additional risk factors for thromboembolism, higher international normalized ratios (INRs) may be targeted.
      • Boyle A.
      Arrhythmias in patients with ventricular assist devices.
      The incidence of ventricular arrhythmias after implantation of an MCS device has been reported to be as high as 22% to 52%.
      • Cesario D.A.
      • Saxon L.A.
      • Cao M.K.
      • et al.
      Ventricular tachycardia in the era of ventricular assist devices.
      • 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).
      Mechanisms of ventricular tachycardia (VT) and ventricular fibrillation (VF) in MCS patients include electrolyte abnormalities, “suction events” caused by overdecompression of the left ventricle and/or cannula positioning, irreversible baseline myopathic substrates prior to implantation, and the potential of new reentrant circuits around the inflow cannula in the apex of the left ventricle.
      • Refaat M.
      • Chemaly E.
      • Lebeche D.
      • et al.
      Ventricular arrhythmias after left ventricular assist device implantation.
      Isolated episodes of VT may be well tolerated, terminated with either antitachycardia pacing from an implantable cardioverter-defibrillator (ICD) or with direct cardioversion. Incessant ventricular arrhythmias, however, lead to poor right ventricular and thereby left ventricular filling, resulting in heart failure, emotional trauma, cardiogenic shock, and even sudden cardiac death. Most patients will have an ICD implanted either before MCS implantation or before discharge. Any hemodynamic change that would allow the inflow cannula to come into contact with myocardial structures, particularly the septal wall, can precipitate VT. Such circumstances include bleeding or hypovolemia due to other causes, increased VAD speeds, and improper angulation of the inflow cannula.
      • Boyle A.
      Arrhythmias in patients with ventricular assist devices.
      On interrogation of the LVAD, one may see low PI numbers indicating ventricular arrhythmias. If a “suction event” is suspected, the VAD speed can be reduced to see if there is improvement, particularly under the guidance of transthoracic echocardiography. Otherwise signs and symptoms of hypovolemia from overdiuresis, bleeding, or dehydration should be investigated. Finally, many patients require antiarrhythmic therapy, most commonly with amiodarone, and need to be followed accordingly.

      Bleeding

      The incidence of GI bleeding in patients with continuous-flow devices is estimated at 20% or more, based on clinical observations and INTERMACS registry data.
      • Slaughter M.S.
      • Rogers J.G.
      • Milano C.A.
      • et al.
      Advanced heart failure treated with continuous-flow left ventricular assist device.
      • Genovese E.A.
      • Dew M.A.
      • Teuteberg J.J.
      • et al.
      Incidence and patterns of adverse event onset during the first 60 days after ventricular assist device implantation.
      • Pagani F.D.
      • Miller L.W.
      • Russell S.D.
      • et al.
      Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device.
      • Kirklin J.K.
      • Naftel D.C.
      • Kormos R.L.
      • et al.
      Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients.
      • Crow S.
      • Chen D.
      • Milano C.
      • et al.
      Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients.
      Bleeding can occur anywhere along the GI tract, as patients are on systemic anticoagulation; however, mechanisms of bleeding unique to continuous-flow devices have been the subject of great interest. It is postulated that relatively high nonphysiologic shear stress is imparted on blood components as they move through the device, which promotes von Willebrand Factor (vWF) proteolysis by the metalloprotease ADAMTS13, leading to a decrease in high molecular weight (functional) vWF multimers.
      • Zaman A.G.
      • Archbold R.A.
      • Helft G.
      • et al.
      Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification.
      • Crow S.
      • Chen D.
      • Milano C.
      • et al.
      Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients.
      • Crow S.
      • Milano C.
      • Joyce L.
      • et al.
      Comparative analysis of von Willebrand factor profiles in pulsatile and continuous left ventricular assist device recipients.
      In addition to an observed acquired von Willebrand disease (vWD), patients are also noted to have a predisposition to the development of angiodysplasia. In fact, up to one-third of LVAD patients have GI bleeding episodes related to angiodysplasia or arteriovenous malformations (AVMs) along the GI tract.
      • Demirozu Z.T.
      • Radovancevic R.
      • Hochman L.F.
      • et al.
      Arteriovenous malformation and gastrointestinal bleeding in patients with the HeartMate II left ventricular assist device.
      Inadequate platelet function and hemostasis caused by acquired vWD in the presence of angiodysplasia make these patients more vulnerable to bleeding. One hypothesis as to why AVMs develop relates to the reduced pulse pressure encountered with continuous-flow devices. The absence of a pulse pressure may lead to intestinal hypoperfusion, causing regional hypoxia, vascular dilation, and subsequent angiodysplasia.
      • Miller L.
      We always need a pulse, or do we??.
      As with management of any case of major GI bleeding, anticoagulation should be acutely stopped and reversed if need be. Patients must be supported hemodynamically with intravenous fluids and blood products as needed. It should be noted, however, that in those patients with MCS as a BTT, frequent transfusions leads to an increased chance for human leukocyte antigen (HLA) sensitization, which may make finding a suitable donor organ more difficult, as well affect posttransplant outcomes.
      • Mehra M.R.
      • Uber P.A.
      • Uber W.E.
      • et al.
      Allosensitization in heart transplantation: implications and management strategies.
      A decision to transfuse that is not emergent should therefore be made in consultation with the transplant cardiology team. Reversing high INR values with vitamin K or fresh frozen plasma must be weighed against the risk of pump thrombosis. Once stabilized, a patient with GI bleeding should be evaluated with upper and lower endoscopy in conjunction with the consultation of a gastroenterologist. If this is unrevealing, a capsule endoscopy or balloon enteroscopy should be performed to assess the small bowel.
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.
      In the setting of persistent bleeding and negative endoscopic evaluation, a tagged red blood scan or angiography can be considered.
      In patients with recurrent GI bleeding and no source amenable to therapy, there is very limited, if any, evidence to support the reduction of LVAD pump speed to allow for less shear stress, increased pulsatility, and potential resolution of AVMs.
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.
      The long-term benefits of octreotide in patients with refractory GI bleeding from small bowel AVMs have been extrapolated for use in the LVAD population.
      • Junquera F.
      • Saperas E.
      • Videla S.
      • et al.
      Long-term efficacy of octreotide in the prevention of recurrent bleeding from gastrointestinal angiodysplasia.
      Further studies are needed to determine whether this strategy is effective.

      Thrombosis

      Although clinically relevant pump thrombosis was noted to be rare in the original HeartMate II trials, in clinical practice the incidence appears to be rising to as much as 10%. Despite the manufacturers’ advised INR target of 1.5 to 2.5 (2–3 in clinical trials) in addition to aspirin, the incidence of pump thrombosis is well reported in the literature.
      • Boyle A.J.
      • Russell S.D.
      • Teuteberg J.J.
      • et al.
      Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: analysis of outpatient anti-coagulation.
      Thrombus may grow from smaller deposits within the pump itself (which can affect flow, power, and PI), or can be consumed directly from the left atrium or left ventricle. Usually the primary indication of pump thrombosis is an increase in power (“power spikes”). PI is also reduced because the pulsatile component of power is decreased relative to the steady component of power required to overcome the burden of thrombus. Clinically, thrombus should also be suspected with hemoglobinuria, increases in lactate dehydrogenase levels to more than 3 times previous levels, or markedly elevated plasma free hemoglobin (usually >40 μmol/L).
      • Slaughter M.S.
      • Pagani F.D.
      • Rogers J.G.
      • et al.
      Clinical management of continuous-flow left ventricular assist devices in advanced heart failure.
      When clinically suspected, additional anticoagulation may be added with heparin or other intravenous anticoagulants. Thrombolytics have been administered locally or systemically on rare occasions with varying success rates, but this strategy remains uncertain and adverse effects are not trivial, particularly intracranial bleeding complications. If thrombosis persists, definitive therapy remains pump exchange in the operating room.
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.
      • Slaughter M.S.
      • Pagani F.D.
      • Rogers J.G.
      • et al.
      Clinical management of continuous-flow left ventricular assist devices in advanced heart failure.
      • Boyle A.J.
      • Russell S.D.
      • Teuteberg J.J.
      • et al.
      Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: analysis of outpatient anti-coagulation.

      Infection

      The most common adverse event accounting for 16.2% of all deaths is infection, as observed in the INTERMACS registry, as well as HeartMate BTT and DT clinical trials.
      • Kirklin J.K.
      • Naftel D.C.
      • Kormos R.L.
      • et al.
      Second INTERMACS annual report: more than 1,000 primary left ventricular assist device implants.
      Infections in MCS device patients are divided into 3 categories: (1) device-specific, involving the pump, cannula, pocket, or percutaneous driveline; (2) device-related, including infective endocarditis, bacteremia, and mediastinitis; and (3) non–device-related.
      • International Society for Heart and Lung Transplantation
      A 2010 working formulation for the standardization of definitions of infections in patients using ventricular assist devices (VADS).
      Patients undergoing MCS implantation are often debilitated from long-standing heart failure and/or cardiogenic shock, with many comorbidities including renal failure, diabetes, malnutrition, and lung disease, conditions all predisposing to infection.
      • Gordon R.J.
      • Quagliarello B.
      • Lowy F.D.
      Ventricular assist device-related infections.
      An early article by Chinn and colleagues
      • Chinn R.
      • Dembitsky W.
      • Eaton L.
      • et al.
      Multicenter experience: prevention and management of left ventricular assist device infections.
      highlights the mainstays of preventing driveline-related infection: (1) immobilization of the percutaneous lead at the exit site is important in preventing disruption of subcutaneous tissue; (2) exit-site care must be executed gently and nontraumatically with meticulous sterile technique, daily or every other day; (3) observation of erythema or increased drainage should prompt investigation and possible hospitalization. Infections may lead to vasodilation and/or sepsis, and may be indicated by increased flows displayed on the monitor. In certain cases of bacteremia, seeding of the device may occur and persist despite intravenous antibiotic therapy, in which case pump exchange may be necessary.
      Secondary antibiotic prophylaxis for dental, respiratory, genitourinary, and gastrointestinal procedures has not been studied in the MCS population. The most recent guidelines state antibiotic prophylaxis would be “reasonable and remains at the discretion of the physician.”
      • Feldman D.
      • Pamboukian S.V.
      • Teuteberg J.J.
      • et al.
      The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary.

      Device Alarms and “Code” Situations

      Health care practitioners responsible for the care of patients with MCS must familiarize themselves with device parameters and their clinical significance. Fig. 6 summarizes the causes of device alarms and potential interventions.
      Figure thumbnail gr6
      Fig. 6Device alarms: causes and potential interventions. LV fcn, left ventricular function; VAD, ventricular assist device.
      It is not uncommon for health care practitioners to react to the frequent absence of a pulse in an LVAD patient, prompting the initiation of Adult Cardiac Life Support (ACLS) protocol. It is particularly important in this population to assess the patient first before reacting to alarms on the display or on telemetry. Patients may often tolerate episodes of VT and VF on an LVAD, and will not require cardioversion. When assessing blood pressure, a Doppler machine must be used to obtain a MAP reading. If an arterial line is placed, it is likely to show a diminished pulse pressure of approximately 15 mm Hg or less. A first step in patient assessment should be to auscultate the left upper abdomen for a continuous LVAD hum. If a continuous humming sound is not appreciated, device malfunction should be suspected and acted upon. If a patient is truly clinically unstable, standard ACLS protocols should be practiced, bearing in mind a pulse cannot be used to monitor status or to dictate appropriate medical therapy. Furthermore, cardiopulmonary resuscitation (CPR) should generally be avoided. Because of the location of the LVAD and its associated connections to myocardial structures, CPR may dislodge components of the device, resulting in fatal bleeding. All emergent situations should involve the urgent consultation of a cardiac surgeon, VAD coordinator, and/or MCS specialized cardiologist. Fig. 7 illustrates a simplified approach to emergency encounters in VAD patients.
      Figure thumbnail gr7
      Fig. 7Approach to emergency encounters in VAD patients. ACLS, Adult Cardiac Life Support; CPR, cardiopulmonary resuscitation; EKG, electrocardiogram; VT/VF, ventricular tachycardia/fibrillation.

      Right Heart Failure and the Need for Biventricular Support

      Selecting appropriate patients for successful MCS involves meeting a multitude of prespecifications, as one would in evaluation for cardiac transplant. These criteria include, but are not limited to, acceptable end-organ function, freedom from active malignancy, freedom from toxic habits, and adequate psychosocial support. Right ventricular failure remains the Achilles heel in MCS, and is associated with higher mortality, greater risk of bleeding, longer hospitalization, and higher rate of renal insufficiency.
      • Miller L.W.
      • Guglin M.
      Patient selection for ventricular assist devices: a moving target.
      • Dang N.C.
      • Topkara V.K.
      • Mercando M.
      • et al.
      Right heart failure after left ventricular assist device implantation in patients with chronic congestive heart failure.
      Many studies have tried to identify markers for the development of right ventricular failure postimplantation, all of which are generally related to end-organ function including vasopressor requirement, elevated liver function tests, creatinine, and blood urea nitrogen, as well as a right ventricular stroke work index of less than 450 mm Hg/ml/m2 and higher central venous pressure.
      • Matthews J.C.
      • Koelling T.M.
      • Pagani F.D.
      • et al.
      The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates.
      • Kormos R.L.
      • Teuteberg J.J.
      • Pagani F.D.
      • et al.
      Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.
      Although the risk of right ventricular failure may also be related to LVAD mechanics itself (discussed earlier), it would seem that the clinical syndrome of right ventricular failure preoperatively is the strongest predictor of right ventricular failure after LVAD implantation. The proportion of patients who suffer right ventricular failure after implantation has decreased but remains at least 5% to 13%.
      • Kormos R.L.
      • Teuteberg J.J.
      • Pagani F.D.
      • et al.
      Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.
      When appropriate, such patients are considered for biventricular MCS as BTT, the mainstay of which has become the CardioWest total artificial heart (TAH) (SynCardia Systems, Inc, Tuscon, AZ). Although the Thoratec paracorporeal VADs can also be used for biventricular support as BTT, their use is limited by large size, higher rates of infection, and poor long-term durability. In other cases, the HeartWare VAD has been used for biventricular support because of its small profile.

      Total artificial heart

      The SynCardia TAH is a pulsatile, implantable pump that consists of 2 polyurethane ventricles with pneumatically driven diaphragms and 4 Medtronic-Hall tilting disc valves (Fig. 8). It is a modern version of the original Jarvik 7, and has since undergone many changes and improvements. Copeland and colleagues
      • Copeland J.G.
      • Smith R.G.
      • Arabia F.A.
      • et al.
      Cardiac replacement with a total artificial heart as a bridge to transplantation.
      • Copeland J.G.
      • Smith R.G.
      • Arabia F.A.
      • et al.
      Total artificial heart bridge to transplantation: a 9-year experience with 62 patients.
      published a seminal article in 2004 showing that the device was effective for bridging 79% of patients with inotrope-refractory biventricular failure to heart transplant. Survival after heart transplant was 86% at 1 year and 64% at 5 years, similar to national registry standards, leading to FDA approval of the device as BTT later that year. Experience with the CardioWest TAH is growing, with nearly 1100 completed in early 2013. Implantation is considered for those not only with biventricular failure from cardiomyopathy but also for those with incessant refractory ventricular arrhythmias, complex congenital heart disease, severe allograft failure after cardiac transplantation, and patients with multiple mechanical valves, severe restrictive cardiomyopathy, or mechanical complications from a large myocardial infarction (such in those complicated by ventricular septal rupture or cardiac rupture). The potential advantage of the TAH is that the entire myopathic substrate is removed from the body, eliminating arrhythmic burden. It also eliminates any chance for myocardial recovery and thus is reserved for bridging patients to transplantation. It use may be considered for lifetime therapy in highly selected patients.
      Figure thumbnail gr8
      Fig. 8SynCardia total artificial heart.
      (Courtesy of syncardia.com.)
      Manufacturers of the CardioWest TAH recommend the device to be reserved for patients with a body surface area of 1.7 m2 or greater, and a thoracic diameter (anterior vertebral body to sternum at 10th thoracic vertebra) of 10 cm or more.
      • Kasirajan V.
      • Tang D.G.
      • Katlaps G.J.
      • et al.
      The total artificial heart for biventricular heart failure and beyond.
      The diaphragm of the pump is activated by movement of air from an external driver, allowing for a maximal stroke volume from each ventricle of 70 mL. Drive pressures for the right and left side are adjusted depending the pulmonary and systemic afterload and volume status. Typical drive pressures for the right pump are between 60 and 90 mm Hg, and between 180 and 200 mm Hg on the left side. The TAH rate is set at greater than 120 beats or ejections per minute, and the percentage of time the pump spends in “systole” is set to 45% to 55%. These parameters are configured to allow for full ejection of blood volume and prevention of stasis, and to prevent clinically significant hemolysis.
      • Copeland J.G.
      • Smith R.G.
      • Arabia F.A.
      • et al.
      Cardiac replacement with a total artificial heart as a bridge to transplantation.
      • Kasirajan V.
      • Tang D.G.
      • Katlaps G.J.
      • et al.
      The total artificial heart for biventricular heart failure and beyond.
      • Mankad A.K.
      • Tang D.G.
      • Clark W.B.
      • et al.
      Persistent anemia after implantation of the total artificial heart.
      Systemic anticoagulation is required with an INR target of 2.5 to 3.5, a higher target attributable to the 4 mechanical valves in the TAH unit.

      Issues unique to the TAH

      Anemia

      It has been observed that TAH patients have a persistent anemia with hematocrit ranging between 18 and 24, presumably because of a combination of chronic hemolysis, ineffective erythropoiesis, and inflammation (predominant). These patients are noted to have markedly elevated lactate dehydrogenase levels (>1000 units/L), undetectable or low haptoglobin levels, and elevated plasma free hemoglobin, as well as elevated high-sensitivity C-reactive protein and reticulocyte production indices.
      • Mankad A.K.
      • Tang D.G.
      • Clark W.B.
      • et al.
      Persistent anemia after implantation of the total artificial heart.

      Portability

      The TAH console is heavy, although selected patients can now be transitioned to the Freedom Driver, which is reasonably convenient and highly portable, allowing for discharge to home. Such portability may allow transition from a BTT-only consideration to DT or lifetime therapy.

      On the horizon

      As technology evolves to bring forth more durable, smaller devices, the selection criteria for appropriate recipients of MCS will expand to encompass a broader, less sick population. The National Heart, Lung, and Blood Institute has initiated the Randomized Evaluation of VAD InterVEntion before Inotropic Therapy study, which is a randomized trial comparing LVAD with optimal medical therapy in patients not yet bound to inotropic therapy. This small-scale proof-of-concept trial will serve to establish the safety of durable MCS in noninotropic therapy–bound advanced heart failure, and provide signals for efficacy in this population.

      New Devices

      Future prospects include a miniaturized LVAD requiring minimally invasive surgery without the need for cardiopulmonary bypass or sternotomy, implanted through the left ventricular apex with a distal cannula in the ascending aorta.
      • Slaughter M.S.
      • Giridharan G.A.
      • Tamez D.
      • et al.
      Transapical miniaturized ventricular assist device: design and initial testing.
      Another concept that shows promise and may transform the MCS field is that of partial circulatory support. The Synergy Pocket micropump device (CircuLite, Inc, Saddle Brook, NJ) is placed off-pump via a minithoracotomy, and has an inflow cannula in the left atrium with the outflow in the right subclavian artery, providing 3 L/min of blood flow.
      • Meyns B.P.
      • Simon A.
      • Klotz S.
      • et al.
      Clinical benefits of partial circulatory support in New York Heart Association Class IIIB and early class IV patients.
      Even as devices reduce in size and improve in durability, and clinicians encounter less morbidity, the need to power such devices with a driveline that exits the skin barrier remains a fundamental limitation. As such, the expansion of durable MCS will be limited until fully implantable systems are made available. The “Holy Grail” for MCS will ultimately be a focus on clinical recovery and explanation of devices rather than the current more narrowly defined indications of lifetime device therapy and bridge to transplant.

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      Linked Article

      • Erratum
        Cardiology ClinicsVol. 32Issue 2
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          An error was made in an article published in the November 2013 issue of Cardiology Clinics (Volume 31, Issue 4) on page 581. “Durable Mechanical Circulatory Support in Advanced Heart Failure: A Critical Care Cardiology Perspective” by Anuradha Lala, MD, and Mandeep R. Mehra, MD, should have included the following disclosure:
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