REVIEW URRENT C OPINION
An update on mechanical circulatory support for heart failure therapy Hadi Daood Toeg a, Talal Al-Atassi a, Jose Perez Garcia b, and Marc Ruel a
Purpose of review This article aims to review contemporary studies that utilized mechanical circulatory support (MCS) in the treatment of heart failure and to elaborate on prospective mechanical alternatives. Recent findings There is a growing need for a well-tolerated, durable and effective MCS option in patients with refractory heart failure. In previous years, the primary indication for MCS therapy supported bridge to transplantation. These early left ventricular assist devices (LVADs) suffered significant adverse events, thereby limiting their prolonged use. With the introduction of newer continuous flow LVADs, with lower morbidity, neurological events, pump failure and the expanded indication use (i.e. destination therapy), the overall number of implanted patients has grown. Summary There has been a dramatic advancement of durability found in the second and third-generation, continuous flow LVADs, along with improved survival rates in patients receiving these devices for destination therapy. MCS may soon become the treatment option of choice in refractory heart failure patients, especially with further evolution of less invasive approaches, smaller designs, and energy sources. Keywords cardiac surgery, heart failure, left ventricular assist device
INTRODUCTION Although heart failure medications along with cardiac resynchronization therapy or implantable cardiac defibrillators have improved quality of life and survival in heart failure patients, overall morbidity and mortality are still high [1]. Refractory end-stage heart failure therapy ultimately requires either short or long-term mechanical circulatory support (MCS) or heart transplantation. Due to lack of available donor hearts or significant comorbidities resulting in contraindication to transplantation, there is a growing need for a well-tolerated, durable and effective MCS option. This article aims to review contemporary studies that utilize MCS in the treatment of heart failure and to elaborate on prospective mechanical alternatives.
LEFT VENTRICULAR ASSIST DEVICE CATEGORIES First-generation left ventricular assist devices (LVADs) included the pulsatile flow MCS devices such as the HeartMate XVE (Thoratec Inc., Pleasanton, California, USA) (Fig. 1), Thoratec PVAD and
the Novacor N100 (WorldHeart Inc., Salt Lake City, Utah, USA) (Table 1). Despite creating a somewhat more physiological profile with pulsatile systemic perfusion, these devices were not durable, were bulky and were prone to significant device malfunction (XVE). Moreover, high stroke rates were observed (Novacor) [2]. Hence, the second-generation LVADs with a continuous axial flow pump system allowed improved durability, smaller size, and less thrombogenicity. These devices include the HeartMate II (HM II; Thoratec Inc., Pleasanton, California, USA) (Fig. 1) and the MicroMed DeBakey (MicroMed Technology Inc., Houston, Texas, USA) (Table 1). With over 250 publications regarding the a
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada and bDivision of Cardiac Surgery, Harvard University, Massachusetts General Hospital, Boston, Massachusetts, USA Correspondence to Marc Ruel, MD, MPH, Division of Cardiac Surgery, University of Ottawa Heart Institute, 3402-40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada. Tel: +1 613 761 4893; fax: +1 613 761 5367; e-mail: [email protected] Curr Opin Cardiol 2014, 29:167–173 DOI:10.1097/HCO.0000000000000037
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KEY POINTS Continuous flow devices are the mainstay for bridge to transplantation or destination therapy. The incidence proportion of the indication for destination therapy is almost equivalent to bridge to transplantation. Short-term mechanical circulatory support is an excellent strategy to temporarily stabilize haemodynamics allowing bridge to decision (or bridge to recovery). New devices must generate adequate cardiac output, be durable, be small in design, and be self-contained (i.e. no driveline for power source).
HM II in the past 12 months, it is no surprise that this is the most widely used LVAD to date. Contemporary results for bridge to transplantation (BTT) by Lok et al. [3] report 1-year survival rates of 81%, 2-year survival rates of 76% and 4-year survival rates of 68%. Alternatively, patients receiving HM IIs for Long term MCS
(a)
(b)
(c)
(d) Venae cavae Right atrium
Right ventricle
HeartMate XVE
HeartMate II
(e)
(f)
HeartWare
Aorta Pulmonary artery Left atrium
Left ventricle
SynCardia TAH
Catheter 9 Fr diameter 5.0 L
Flow rate up to 5.0 L/min Blood inlet area
21Fr pump motor
Outlet area April 2009, received FDA 510(k) clearance
CentriMag
Impella
Short term MCS
FIGURE 1. Images of commonly used contemporary durable (long-term) or short-term mechanical circulatory support devices. First-generation device (a) Thoratec HeartMate XVE: pulsatile flow LVAD (left ventricular assist device) (reprinted with the permission of Thoratec Incorporation). Secondgeneration LVAD (b) Thoratec HeartMate II (reprinted with the permission of Thoratec Incorporation). Third-generation LVAD (c) HeartWare HVAD (reprinted with the permission of HeartWare). Approved TAH (d) SynCardia CardioWest TAH (courtesy: SynCardia.com). Short-term MCS devices with (e) Levitronix CentriMag extracorporeal RVAD (reprinted with the permission of Thoratec Incorporation), and the (f) AbioMed Impella 5.0 (reprinted with the permission of Abiomed). RVAD, right ventricular assist device; TAH, total artificial heart. 168
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destination therapy had similar clinical outcomes, with 1-year survival rates of 73% [4]. The third-generation LVADs minimize contact between the pump and the axial or centrifugal rotor by using magnetic levitation technology, thereby reducing friction and wear of the device. Thirdgeneration LVADs include the DuraHeart (Terumo Heart Inc., Ann Arbor, Michigan, USA), Incor (Berlin Heart Inc., Berlin, Germany), HeartWare HVAD (HeartWare International Inc., Framingham, Massachusetts, USA) (Fig. 1) and the recently discontinued Levacor (WorldHeart Inc., Salt Lake City, Utah, USA) (Table 1). Centrifugal third-generation devices (radial flow devices) are advantageous to secondgeneration LVADs due to their requirement for lower rotational speeds, enhanced anatomic design, and overall efficiency. The HeartWare HVAD is a centrifugal magnetically levitated pump system with an extremely small design allowing implantation in the pericardial space. In November 2012, after results from the ADVANCE trial (Evaluation of the HeartWare LVAD for the Treatment of Advanced Heart Failure) demonstrating similar survival rates after 180 days when compared with contemporary controls, the HeartWare HVAD was approved by the US Food and Drugs Administration (FDA) for BTT [5]. Furthermore, the completed ENDURANCE trial (a Clinical Trial to Evaluate the HeartWare Ventricular Assist System) will determine whether the HeartWare HVAD can be used with similar effectiveness to the HM II for destination therapy (ClinicalTrials. gov.Identifier: NCT01166347; data pending). Although the Incor is currently approved for European use for BTT and destination therapy, it is still considered an investigational LVAD in the United States. Finally, the DuraHeart, a LVAD used more in European nations, has survival rates comparable to HM II, with 77% at 1 year and 61% at 2 years [6]. Despite 40 years of research in the quest for finding the total artificial heart (TAH), only two survived to regulatory level trials (SynCardia; SynCardia Systems Inc., Tucson, Arizona, USA, and Abiocor TAH; Abiomed, Danvers, Massachusetts, USA) (Fig. 1). Patients receiving the SynCardia had higher survival to transplantation, 1-year survival and 5-year survival than control patients (79 versus 46%, P < 0.001; 86 versus 69%; and 64 versus 34%, respectively) [7]. In a recent postmarket approval study to determine whether results from the multicentre trial were translatable, Slepian et al. [8 ] demonstrated similar results in the hands of a variety of surgeons and from different centres [9]. Thus, the optimal strategy for refractory heart failure patients not amenable for heart transplantation should include implanting the ideal MCS &&
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Mechanical support for heart failure therapy Toeg et al. Table 1. List of contemporary ventricular assist devices used for either short-term or long-term mechanical circulatory support (Manufacturer) Device
Mechanism
Type
Duration
Approvala
Indication
Position
(Thoratec) PVAD
Pulsatile
Intra
Short
Yes
BTT, BTR
R, L or bilateral
(World Heart) Novocor
Pulsatile
Intra
Long
Yes
BTT, DT
L
(Thoratec) HeartMate XVE
Pulsatile
Intra
Long
Yes
BTT, DT
L
(BerlinHeart) EXCOR
Pulsatile
Para
Long
Yes
BTTb
R, L or bilateral
(Thoratec) HeartMate II
Continuous axial
Intra
Long
Yes
BTT, DT
L b
(MicroMed) DeBakey HeartAssist 5
Continuous axial
Intra
Long
Yes
BTT, BTR
L
(HeartWare) HVAD
Continuous centrifugal
Intra
Long
Yes
BTT
L
(Terumo) DuraHeart
Continuous centrifugal
Intra
Long
Investigational
BTT
L
(BerlinHeart) INCOR
Continuous axial
Intra
Long
Investigational
BTT
L
(Jarvik) FlowMaker
Continuous axial
Intra
Long
Investigational
BTT
L
Extracorporeal membrane oxygenation, ECMO
Continuous centrifugal/axial
Extra
Short
Yes
BTR, BTD
Bilateral
(Levitronix) CentriMag
Continuous centrifugal
Extra
Short
Yes
BTR, BTD
R, L or bilateral
(AbioMed) Impella
Continuous axial
Perc
Short
Yes
BTR, BTD
L
(CardiacAssist) TandemHeart
Continuous centrifugal
Perc
Short
Investigational
BTR, BTD
L
(Maquet) RotaFlow
Continuous centrifugal
Extra
Short
Investigational
BTR, BTD
R, L or bilateral
(SynCardia) CardioWest TAH
Pulsatile
Intra
Long
Yes
BTT
Bilateral
(AbioMed) Abiocor TAH
Pulsatile
Intra
Long
Investigational
BTT
Bilateral
BTD, bridge to decision; BTR, bridge to recovery; BTT, bridge to transplantation; DT, destination therapy; Extra, extracorporeal; Intra, intracorporeal; L, left; Para, paracorporeal; Perc, percutaneously placed; PVAD, paracorporeal ventricular assist device; R, right; TAH, total artificial heart. a Federal Drug Administration approval status. b Indicated for paediatric population.
device with greatest durability and lowest incidence of adverse events and that provides satisfactory cardiac output for either one or both failing ventricles.
TRENDS IN LEFT VENTRICULAR ASSIST DEVICE USE AND OUTCOMES The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is the largest registry of MCS device utilization, with 145 participating hospitals. The most recent fifth INTERMACS annual report presents MCS data from 23 June 2006 to 30 June 2012. Durable MCS devices were used in 6885 patients, with 243 having a previous MCS device, 72 being paediatric patients and nine having an isolated right ventricular assist device (RVAD) [10]. Of the 6561 patients with primary implant for left ventricular support, 136 received a TAH, 910 received a pulsatile flow LVAD (68.1% LVAD only) and the remaining 5515 received a continuous flow LVAD (97.3% LVAD only) for BTT or destination therapy. Survival for all comers with a continuous flow LVAD was 80% at 1 year and 70% at 2 years. Furthermore, Park et al. [4] report similar 1-year survival rates with the exclusive use of HM II for destination therapy at 73% along with a significant reduction in haemorrhagic stroke-related deaths.
Prior to 2011, the majority of patients were listed as either BTT (patient currently listed for heart transplantation) or bridge to transplant candidacy/eligibility (likely BTT) with 65.4%, while destination therapy accounted for only 18.4% [10]. These trends have dramatically changed, starting in 2010 when the HM II was FDA approved for destination therapy. Thus, in 2011, BTT strategy dropped to 45% whereas destination therapy increased to 38.9% [10]. These trends continue into mid-2012, with BTT accounting for 42.8% and destination therapy accounting for 44% [10]. Moreover, indication for bridge to transplant candidacy or eligibility, which consists of sustained ventricular support in hopes of altering modifiable contraindications (i.e. renal dysfunction, high body mass index and pulmonary hypertension), has remained steady for LVAD indication at 24% [10]. With the advancement of LVAD technology, perioperative care and patient selection, these trends will likely continue and perhaps the number of patients for bridge to candidacy will increase, as the number of heart failure patients is increasing with a stagnant heart donor pool. In the INTERMACS report, freedom from device exchange or death related to device malfunction was similar for pulsatile and continuous flow devices for the first 8 months (96%); however, a significant linear decrease in the freedom from device
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malfunction in the pulsatile device group was seen after 8 months until 24 months (40%, P < 0.0001) as compared with the relatively steady freedom of device issue at 24 months in the continuous flow LVAD (94%) [10]. Furthermore, on the basis of competing outcomes (cardiac transplantation, death survival on MCS device and recovery) in another contemporary report, patients receiving pulsatile flow LVADs were less likely to be alive at 12 months (31%) when compared with continuous flow LVADs at 12 months (54%) [11]. In addition to improved survival, quality of life, general well being and ability to perform self-care significantly improved and remained steady out to 12 months post-LVAD implantation [4,10]. Albeit a small retrospective survey study, sexual function overall was reported worse at 12 months postcontinuous flow LVAD implant, which may be attributed more to psychological issues such as fear of damaging the device and self/partner harm [12]. Finally, although the left ventricle is typically intact, the term LVAD is a relative misnomer, as most devices are being implanted to physiologically replace the function of the left heart (i.e. left heart replacement).
LEFT VENTRICULAR ASSIST DEVICE COMPLICATIONS When considering MCS versus heart transplantation for heart failure therapy, one needs to evaluate the complications associated with each strategy: MCS therapy complications include stroke, bleeding, infection and device malfunction, while heart transplantation complications include rejection, infection, malignancy and allograft vasculopathy. Although survival free of stroke is high at 12 and 24 months with MCS, the actuarial freedom from any major adverse event including infection, bleeding, device malfunction, stroke or death is quite low, with 30% at 12 months and 19% at 24 months irrespective of age and INTERMACS level (see Table 2) [10,13,14]. Rate of device failure over time
represents the MCS engineering measure of durability, which can result from either a mechanical issue (motor failure) or a biological one (device thrombosis or haemolysis). Pump failure may lead to significant clinical outcomes including death, stroke, bleeding, infection and redo-surgery for pump exchange, which in a recent study was shown to afflict 17% of patients requiring pump change for device failure [15]. Furthermore, readmission rates for continuous flow LVAD patients remain high at 1.64 1.97 admissions per patient-year follow up [16 ]. A recent prospective multicentre study [17] reported that 22% of HM II patients had an infection, with the driveline site being the most common and Staphylococci being the most common pathogen (47%), and that a history of depression and elevated serum creatinine were independent predictors of device infection. Alternatively, the most common reason for readmission is due to bleeding, mainly from the gastrointestinal tract [16 ]. It has been hypothesized that continuous flow devices (HM II or HeartWare HVAD), with low or nonpulsatile flow characteristics, replicate the mechanism of aortic stenosis. This leads to colonic mucosal ischaemia along with high shear stress, resulting in acquired von Willebrands disease, arteriovenous malformations and thus gastrointestinal bleeding [5,18–20]. Although acquired von Willebrands dysfunction may be a likely contributor to LVAD-related gastrointestinal bleeding, the true mechanism is likely multifactorial, with oral anticoagulation use, age and previous history of gastrointestinal bleeding being a few known risk factors [19,21]. Nevertheless, when comparing adverse events between pulsatile and continuous flow MCS devices, it is quite evident that pulsatile devices have increased rates of adverse events in all categories. Specifically, the rate for device malfunction expressed as events per 100 patient-months is 3.26 in the pulsatile group compared with 1.60 in the continuous group (P < 0.0001). Also, bleeding and infection rates are significantly higher in the &&
&&
Table 2. INTERMACS clinical profile levels INTERMACS level
Title
Clinical description
1
Cardiogenic shock
Life-threatening hypotension with escalating inotropic and vasopressor support
2
Progressive decline
Despite inotropic support still demonstrates continued deterioration
3
Stable with inotropes
Stable on moderate inotropic support or temporary mechanical circulatory support
4
Resting symptoms
Patient at home on optimal medical therapy but frequently has NYHA IV symptoms
5
Exertion intolerant
Patient comfortable at rest but unable to engage in any activity
6
Exertion limited
Patient comfortable at rest and able to do very mild activity
7
Advanced NYHA III
Despite history of previous decompensation, patient comfortable at mild activity
NYHA, New York Heart Association. Adapted with permission [13,14].
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pulsatile group (17.28 and 22.81, respectively) versus the continuous group (9.45 and 8.01, respectively; P < 0.0001) [10]. Thus, it is no wonder that, as of 2009 and onwards, more than 85% of all implanted devices for BTT or destination therapy were continuous flow MCS devices. Moreover, from 2010 onwards, nearly 100% of patients for destination therapy received continuous flow LVADs [10].
blood via an outflow arterial cannula. Although survival rates utilizing ECMO in refractory cardiogenic shock patients vary regarding clinical indication, with survival to discharge ranging from 39 to 80% [23,24], the lack of durability (limited to days, with mean of 3.8 days) and the bleeding/coagulopathic issues surrounding vascular access are major shortcomings of this intervention [23,25,26].
LEFT VENTRICULAR ASSIST DEVICE SELECTION
Extracorporeal mechanical circulatory support
After patient selection and optimization are achieved, MCS device selection should then be tailored according to patient’s expectations and general clinical status and upon recommendations from a multidisciplinary approach. Patients who are haemodynamically stable or classified as INTERMACS 3 or greater can be considered for BTT or destination therapy. In both instances, a durable, long-term MCS device such as the HM II, HeartWare HVAD or Abiomed AB5000 is the device of choice (Table 2). If the patient is haemodynamically unstable or progressively declining (INTERMACS 1 or 2), short-term MCS therapy should be immediately considered (Table 2). This buys the heart failure team time to make a decision for further management [bridge to decision (BTD)] or can provide the patient with essential circulatory support for myocardial recovery.
Some of the older extracorporeal MCS devices used include the Abiomed BVS5000 (Abiomed Inc., Danvers, Massachusetts, USA), a nondurable pulsatile pneumatically driven device, the Abiomed AB5000, and the Thoratec Paracorporeal Ventricular Assist Device II. More recently, the Levitronix CentriMag (Levitronix LLC/Thoratec Inc., Waltham, Massachusetts, USA) (Fig. 1), a third-generation device that uses a magnetically levitated rotary pump designed for temporary extracorporeal support (flow rates up to 10 l/min), is used in patients with postcardiotomy shock, allograft failure, right ventricular failure with existing LVAD and refractory heart failure after acute myocardial infarction. Although the FDA has approved CentriMag for providing temporary right ventricular support after LVAD insertion for up to 30 days, several studies have used the CentriMag for more than 100 days with no increased incidence of thromboembolic complications [27]. Loforte et al. [28] describe their 1 and 2-year survival results with this device in 42 patients with the majority in postcardiotomy shock or right ventricular failure after LVAD placement (55 and 24%, respectively). This approach created a BTD by temporarily establishing adequate systemic perfusion and altering the patient’s INTERMACS profile (Table 2) [29].
SHORT-TERM LEFT VENTRICULAR ASSIST DEVICE OR RIGHT VENTRICULAR ASSIST DEVICE OPTIONS: INTRA-AORTIC BALLOON PUMP Intra-aortic balloon pump (IABP) is commonly used as the first mechanical support treatment in efforts to improve coronary perfusion in the setting of refractory cardiogenic shock. Although some patients may benefit from IABP versus other forms of MCS, a recent randomized controlled trial comparing IABP with controls (best medical therapy) demonstrated similar 30-day mortality and major adverse events [22]. Thus, more research is needed to determine in which clinical setting it would be advantageous to use IABP.
Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation (ECMO) is a rapid, easy to initiate mode of emergency biventricular support. This system provides excellent haemodynamic support via a nonpulsatile pump, membrane oxygenator that receives blood via inflow venous cannulas and returns oxygenated
Percutaneous mechanical circulatory support With the advancement of MCS technology, percutaneous insertion of LVADs can be achieved with devices such as the Impella LP (Abiomed) (Fig. 1) and the TandemHeart (CardiacAssist, Pittsburgh, Pennsylvania, USA). Although the main indication for utilization of percutaneous LVADs is for highrisk percutaneous coronary intervention, these miniaturized LVADs have been used to provide adequate perfusion (2.5–5 l/min) in some patients with acute transient haemodynamic instability such as myocarditis, or allograft rejection. Cardiogenic shock may result from biventricular failure, thereby increasing the demand for RVAD. After haemodynamic stability is achieved via nondurable MCS therapy, clinicians must continuously evaluate and
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consider weaning from this short-term strategy or proceeding to long-term MCS. Impella devices are approved for up to 7 days; however, some centres maintain patients on Impella support for up to 27 days (mean ¼ 14.2 days) by means of a right axillary approach [30–32]. Although guidelines are still being updated, it is common practice to reduce the MCS flows by 0.5 l/min and assess the following: clinical status, native left ventricular contraction, ancillary blood work (lactate) and echocardiography [33].
LVAD technology, surgical methods and postoperative management: Goldstein et al. [39] present an in-depth algorithm for diagnosing and treating LVAD thrombosis, a serious complication following LVAD insertion. Lastly, mounting evidence suggests that allowing the native aortic valve to open at least 50% of the time (achieving a pulse pressure >15 mmHg) may minimize the incidence of de-novo aortic insufficiency [40–42] likely due to commissural fusion of the valve leaflets [43].
CONCLUSION FUTURE CONCEPTS The HeartWare miniaturized VAD is a new, smaller continuous axial flow pump, with the same magnetically driven ‘contactless’ impeller, that will likely begin clinical trials in 2013. Along with this ultraminiature design (available as RVAD), this company is researching the use of transcutaneous energy transfer technology in efforts to discontinue the need for a driveline-mediated energy source. Also, Thoratec Inc. is conducting research and development for a third-generation LVAD (HeartMate 3) that is ultracompact and magnetically levitated and has the ability to induce pulsatility. The CARMAT heart, a bovine bioprosthetic heart mimicking the heart’s ventricles, will begin clinical trials this year in medical centres across Europe and the Middle East. This TAH is unique, with a lined bovine pericardial tissue to reduce the incidence of clotting, and is embedded with microsensors to adjust blood flow in response to patients’ needs. Finally, miniaturized percutaneous pumps (Impella, TandemHeart) to assist either the left or the right ventricle may supplement current larger LVADs by providing 2–3.5 l/min of cardiac output. These devices have already been implanted via an axillary approach, allowing patient ambulation and return of normal functioning [31]. Also, the SYNERGY (CircuLite Inc., Teaneck, New Jersey, USA) micropump surgical system providing 4.25 l/min of flow has received FDA conditional approval to undergo a feasibility trial enrolling patients in INTERMACs level of at least 4 (Table 2). Management guidelines for LVAD patients are continually being updated, with more centres reporting their results [10,34,35]. Some relative contraindications to LVAD insertion include acute cardiogenic shock with uncertain neurological status, active severe bleeding, active uncontrolled systemic infection, severe right ventricular dysfunction, severe aortic insufficiency that will not be corrected or mechanical aortic valve that will not be converted to a bioprosthesis [35–38]. These contraindications will change with improvement in 172
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It is clear that to achieve better outcomes for our patients with significant heart failure, a mechanical condition, we need to utilize a mechanical intervention. Heart transplantation is the gold standard and provides exceptional long-term results, but is limited based on the stagnant donor pool and the increasing complexity of patient comorbidities, thereby leading to heart transplantation contraindications. There has been dramatic advancement of durability found in the second and third-generation, continuous flow LVADs, along with improved survival rates in patients receiving these devices for destination therapy. MCS may soon become the treatment option of choice in refractory heart failure patients, especially with further evolution of less invasive approaches, smaller designs, and energy sources. Acknowledgements None. Conflicts of interest M.R. received research support and honoraria from Medtronic Inc.
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Mechanical support for heart failure therapy Toeg et al. 6. Morshuis M, El-Banayosy A, Arusoglu L, et al. European experience of DuraHeart magnetically levitated centrifugal left ventricular assist system. Eur J Cardiothorac Surg 2009; 35:1020–1027; discussion 1027–1028. 7. Copeland JG, Smith RG, Arabia FA, et al. Cardiac replacement with a total artificial heart as a bridge to transplantation. N Engl J Med 2004; 351:859– 867. 8. Slepian MJ, Alemu Y, Girdhar G, et al. The Syncardia total artificial heart: in && vivo, in vitro, and computational modeling studies. J Biomechanics 2013; 46:266–275. An important article that describes the most recent trends in MCS therapy. 9. Kirsch ME, Nguyen A, Mastroianni C, et al. SynCardia temporary total artificial heart as bridge to transplantation: current results at la pitie hospital. Ann Thorac Surg 2013; 95:1640–1646. 10. Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6000 mechanical circulatory support patients. J Heart Lung Transplant 2013; 32:141–156. 11. Holman WL, Naftel DC, Eckert CE, et al. Durability of left ventricular assist devices: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 2006 to 2011. J Thorac Cardiovasc Surg 2013; 146:437– 441. 12. Eckman P, Dhungel V, Mandras S, et al. Sexual function after left ventricular assist device. J Am Coll Cardiol 2013; 61:2021–2022. 13. Barge-Caballero E, Paniagua-Martin MJ, Marzoa-Rivas R, et al. Usefulness of the INTERMACS Scale for predicting outcomes after urgent heart transplantation. Rev Esp Cardiol 2011; 64:193–200. 14. Kirklin JK, Naftel DC, Kormos RL, et al. The Fourth INTERMACS Annual Report: 4000 implants and counting. J Heart Lung Transplant 2012; 31:117– 126. 15. Stephenson E, El-Banayosy A, Soleimani B. Incidence of pump failure and change in continuous flow left ventricular assist devices [Abstract]. 93rd AATS meeting, Minneapolis, MN, US, 7 May 2013. 16. 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. A useful study reporting the incidence and cause of MCS infections and common ways to treat or prevent these complications. 17. Gordon RJ, Weinberg AD, Pagani FD, et al. Prospective, multicenter study of ventricular assist device infections. Circulation 2013; 127:691–702. 18. Uriel N, Pak SW, Jorde UP, et al. Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J Am Coll Cardiol 2010; 56:1207–1213. 19. Klovaite J, Gustafsson F, Mortensen SA, et al. Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). J Am Coll Cardiol 2009; 53:2162–2167. 20. Demirozu ZT, Radovancevic R, Hochman LF, et al. Arteriovenous malformation and gastrointestinal bleeding in patients with the HeartMate II left ventricular assist device. J Heart Lung Transplant 2011; 30:849–853. 21. Muthiah K, Robson D, Macdonald PS, et al. Increased incidence of angiodysplasia of the gastrointestinal tract and bleeding in patients with continuous flow left ventricular assist devices (LVADs). Int J Artif Organs 2013; 36:449– 454. 22. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012; 367: 1287–1296. 23. Paden ML, Conrad SA, Rycus PT, et al. Extracorporeal Life Support Organization Registry Report 2012. ASAIO J 2013; 59:202–210. 24. Prodhan P, Bhutta AT, Gossett JM, et al. Comparative effects of ventricular assist device and extracorporeal membrane oxygenation on renal function in pediatric heart failure. Ann Thorac Surg 2013; 96:1428–1434.
25. Shin TG, Choi J-H, Jo IJ, et al. Extracorporeal cardiopulmonary resuscitation in patients with inhospital cardiac arrest: a comparison with conventional cardiopulmonary resuscitation. Crit Care Med 2011; 39:1–7. 26. Aziz F, Brehm CE, El-Banyosy A, et al. Arterial complications in patients undergoing extracorporeal membrane oxygenation via femoral cannulation. Ann Vasc Surg 2013. [Epub ahead of print] 27. Haj-Yahia S, Birks EJ, Amrani M, et al. Bridging patients after salvage from bridge to decision directly to transplant by means of prolonged support with the CentriMag short-term centrifugal pump. J Thorac Cardiovasc Surg 2009; 138:227–230. 28. Loforte A, Montalto A, Ranocchi F, et al. Levitronix CentriMag third-generation magnetically levitated continuous flow pump as bridge to solution. ASAIO J 2011; 57:247–253. 29. John R, Liao K, Lietz K, et al. Experience with the Levitronix CentriMag circulatory support system as a bridge to decision in patients with refractory acute cardiogenic shock and multisystem organ failure. J Thorac Cardiovasc Surg 2007; 134:351–358. 30. Lemaire A, Anderson MB, Prendergast T, et al. Outcome of the impella device for acute mechanical circulatory support. Innovations (Phila) 2013; 8:12–16. 31. Pozzi M, Quessard A, Nguyen A, et al. Using the Impella 5.0 with a right axillary artery approach as bridge to long-term mechanical circulatory assistance. Int J Artif Organs 2013; 36:605–611. 32. Sassard T, Scalabre A, Bonnefoy E, et al. The right axillary artery approach for the Impella Recover LP 5.0 microaxial pump. Ann Thorac Surg 2008; 85:1468–1470. 33. 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; 126:2648–2667. 34. 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 (Suppl 4):S1–S39. 35. Feldman D, Pamboukian SV, Teuteberg JJ, et al. The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary. J Heart Lung Transplant 2013; 32:157– 187. 36. Khazanie P, Rogers JG. Patient selection for left ventricular assist devices. Congest Heart Fail 2011; 17:227–234. 37. Slaughter MS, Meyer AL, Birks EJ. Destination therapy with left ventricular assist devices: patient selection and outcomes. Curr Opin Cardiol 2011; 26:232–236. 38. Lund LH, Matthews J, Aaronson K. Patient selection for left ventricular assist devices. Eur J Heart Failure 2010; 12:434–443. 39. Goldstein DJ, John R, Salerno C, et al. Algorithm for the diagnosis and management of suspected pump thrombus. J Heart Lung Transplant 2013; 32:667–670. 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. Hatano M, Kinugawa K, Shiga T, et al. Less frequent opening of the aortic valve and a continuous flow pump are risk factors for postoperative onset of aortic insufficiency in patients with a left ventricular assist device. Circ J 2011; 75:1147–1155. 42. Bishop CJ, Mason NO, Kfoury AG, et al. A novel noninvasive method to assess aortic valve opening in HeartMate II left ventricular assist device patients using a modified Karhunen-Loeve transformation. J Heart Lung Transplant 2010; 29:27–31. 43. Martina JR, Schipper ME, de Jonge N, et al. Analysis of aortic valve commissural fusion after support with continuous-flow left ventricular assist device. Interact Cardiovasc Thorac Surg 2013; 17:616–624.
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An update on mechanical circulatory support for heart failure therapy Hadi Daood Toeg a, Talal Al-Atassi a, Jose Perez Garcia b, and Marc Ruel a
Purpose of review This article aims to review contemporary studies that utilized mechanical circulatory support (MCS) in the treatment of heart failure and to elaborate on prospective mechanical alternatives. Recent findings There is a growing need for a well-tolerated, durable and effective MCS option in patients with refractory heart failure. In previous years, the primary indication for MCS therapy supported bridge to transplantation. These early left ventricular assist devices (LVADs) suffered significant adverse events, thereby limiting their prolonged use. With the introduction of newer continuous flow LVADs, with lower morbidity, neurological events, pump failure and the expanded indication use (i.e. destination therapy), the overall number of implanted patients has grown. Summary There has been a dramatic advancement of durability found in the second and third-generation, continuous flow LVADs, along with improved survival rates in patients receiving these devices for destination therapy. MCS may soon become the treatment option of choice in refractory heart failure patients, especially with further evolution of less invasive approaches, smaller designs, and energy sources. Keywords cardiac surgery, heart failure, left ventricular assist device
INTRODUCTION Although heart failure medications along with cardiac resynchronization therapy or implantable cardiac defibrillators have improved quality of life and survival in heart failure patients, overall morbidity and mortality are still high [1]. Refractory end-stage heart failure therapy ultimately requires either short or long-term mechanical circulatory support (MCS) or heart transplantation. Due to lack of available donor hearts or significant comorbidities resulting in contraindication to transplantation, there is a growing need for a well-tolerated, durable and effective MCS option. This article aims to review contemporary studies that utilize MCS in the treatment of heart failure and to elaborate on prospective mechanical alternatives.
LEFT VENTRICULAR ASSIST DEVICE CATEGORIES First-generation left ventricular assist devices (LVADs) included the pulsatile flow MCS devices such as the HeartMate XVE (Thoratec Inc., Pleasanton, California, USA) (Fig. 1), Thoratec PVAD and
the Novacor N100 (WorldHeart Inc., Salt Lake City, Utah, USA) (Table 1). Despite creating a somewhat more physiological profile with pulsatile systemic perfusion, these devices were not durable, were bulky and were prone to significant device malfunction (XVE). Moreover, high stroke rates were observed (Novacor) [2]. Hence, the second-generation LVADs with a continuous axial flow pump system allowed improved durability, smaller size, and less thrombogenicity. These devices include the HeartMate II (HM II; Thoratec Inc., Pleasanton, California, USA) (Fig. 1) and the MicroMed DeBakey (MicroMed Technology Inc., Houston, Texas, USA) (Table 1). With over 250 publications regarding the a
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada and bDivision of Cardiac Surgery, Harvard University, Massachusetts General Hospital, Boston, Massachusetts, USA Correspondence to Marc Ruel, MD, MPH, Division of Cardiac Surgery, University of Ottawa Heart Institute, 3402-40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada. Tel: +1 613 761 4893; fax: +1 613 761 5367; e-mail: [email protected] Curr Opin Cardiol 2014, 29:167–173 DOI:10.1097/HCO.0000000000000037
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KEY POINTS Continuous flow devices are the mainstay for bridge to transplantation or destination therapy. The incidence proportion of the indication for destination therapy is almost equivalent to bridge to transplantation. Short-term mechanical circulatory support is an excellent strategy to temporarily stabilize haemodynamics allowing bridge to decision (or bridge to recovery). New devices must generate adequate cardiac output, be durable, be small in design, and be self-contained (i.e. no driveline for power source).
HM II in the past 12 months, it is no surprise that this is the most widely used LVAD to date. Contemporary results for bridge to transplantation (BTT) by Lok et al. [3] report 1-year survival rates of 81%, 2-year survival rates of 76% and 4-year survival rates of 68%. Alternatively, patients receiving HM IIs for Long term MCS
(a)
(b)
(c)
(d) Venae cavae Right atrium
Right ventricle
HeartMate XVE
HeartMate II
(e)
(f)
HeartWare
Aorta Pulmonary artery Left atrium
Left ventricle
SynCardia TAH
Catheter 9 Fr diameter 5.0 L
Flow rate up to 5.0 L/min Blood inlet area
21Fr pump motor
Outlet area April 2009, received FDA 510(k) clearance
CentriMag
Impella
Short term MCS
FIGURE 1. Images of commonly used contemporary durable (long-term) or short-term mechanical circulatory support devices. First-generation device (a) Thoratec HeartMate XVE: pulsatile flow LVAD (left ventricular assist device) (reprinted with the permission of Thoratec Incorporation). Secondgeneration LVAD (b) Thoratec HeartMate II (reprinted with the permission of Thoratec Incorporation). Third-generation LVAD (c) HeartWare HVAD (reprinted with the permission of HeartWare). Approved TAH (d) SynCardia CardioWest TAH (courtesy: SynCardia.com). Short-term MCS devices with (e) Levitronix CentriMag extracorporeal RVAD (reprinted with the permission of Thoratec Incorporation), and the (f) AbioMed Impella 5.0 (reprinted with the permission of Abiomed). RVAD, right ventricular assist device; TAH, total artificial heart. 168
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destination therapy had similar clinical outcomes, with 1-year survival rates of 73% [4]. The third-generation LVADs minimize contact between the pump and the axial or centrifugal rotor by using magnetic levitation technology, thereby reducing friction and wear of the device. Thirdgeneration LVADs include the DuraHeart (Terumo Heart Inc., Ann Arbor, Michigan, USA), Incor (Berlin Heart Inc., Berlin, Germany), HeartWare HVAD (HeartWare International Inc., Framingham, Massachusetts, USA) (Fig. 1) and the recently discontinued Levacor (WorldHeart Inc., Salt Lake City, Utah, USA) (Table 1). Centrifugal third-generation devices (radial flow devices) are advantageous to secondgeneration LVADs due to their requirement for lower rotational speeds, enhanced anatomic design, and overall efficiency. The HeartWare HVAD is a centrifugal magnetically levitated pump system with an extremely small design allowing implantation in the pericardial space. In November 2012, after results from the ADVANCE trial (Evaluation of the HeartWare LVAD for the Treatment of Advanced Heart Failure) demonstrating similar survival rates after 180 days when compared with contemporary controls, the HeartWare HVAD was approved by the US Food and Drugs Administration (FDA) for BTT [5]. Furthermore, the completed ENDURANCE trial (a Clinical Trial to Evaluate the HeartWare Ventricular Assist System) will determine whether the HeartWare HVAD can be used with similar effectiveness to the HM II for destination therapy (ClinicalTrials. gov.Identifier: NCT01166347; data pending). Although the Incor is currently approved for European use for BTT and destination therapy, it is still considered an investigational LVAD in the United States. Finally, the DuraHeart, a LVAD used more in European nations, has survival rates comparable to HM II, with 77% at 1 year and 61% at 2 years [6]. Despite 40 years of research in the quest for finding the total artificial heart (TAH), only two survived to regulatory level trials (SynCardia; SynCardia Systems Inc., Tucson, Arizona, USA, and Abiocor TAH; Abiomed, Danvers, Massachusetts, USA) (Fig. 1). Patients receiving the SynCardia had higher survival to transplantation, 1-year survival and 5-year survival than control patients (79 versus 46%, P < 0.001; 86 versus 69%; and 64 versus 34%, respectively) [7]. In a recent postmarket approval study to determine whether results from the multicentre trial were translatable, Slepian et al. [8 ] demonstrated similar results in the hands of a variety of surgeons and from different centres [9]. Thus, the optimal strategy for refractory heart failure patients not amenable for heart transplantation should include implanting the ideal MCS &&
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Mechanical support for heart failure therapy Toeg et al. Table 1. List of contemporary ventricular assist devices used for either short-term or long-term mechanical circulatory support (Manufacturer) Device
Mechanism
Type
Duration
Approvala
Indication
Position
(Thoratec) PVAD
Pulsatile
Intra
Short
Yes
BTT, BTR
R, L or bilateral
(World Heart) Novocor
Pulsatile
Intra
Long
Yes
BTT, DT
L
(Thoratec) HeartMate XVE
Pulsatile
Intra
Long
Yes
BTT, DT
L
(BerlinHeart) EXCOR
Pulsatile
Para
Long
Yes
BTTb
R, L or bilateral
(Thoratec) HeartMate II
Continuous axial
Intra
Long
Yes
BTT, DT
L b
(MicroMed) DeBakey HeartAssist 5
Continuous axial
Intra
Long
Yes
BTT, BTR
L
(HeartWare) HVAD
Continuous centrifugal
Intra
Long
Yes
BTT
L
(Terumo) DuraHeart
Continuous centrifugal
Intra
Long
Investigational
BTT
L
(BerlinHeart) INCOR
Continuous axial
Intra
Long
Investigational
BTT
L
(Jarvik) FlowMaker
Continuous axial
Intra
Long
Investigational
BTT
L
Extracorporeal membrane oxygenation, ECMO
Continuous centrifugal/axial
Extra
Short
Yes
BTR, BTD
Bilateral
(Levitronix) CentriMag
Continuous centrifugal
Extra
Short
Yes
BTR, BTD
R, L or bilateral
(AbioMed) Impella
Continuous axial
Perc
Short
Yes
BTR, BTD
L
(CardiacAssist) TandemHeart
Continuous centrifugal
Perc
Short
Investigational
BTR, BTD
L
(Maquet) RotaFlow
Continuous centrifugal
Extra
Short
Investigational
BTR, BTD
R, L or bilateral
(SynCardia) CardioWest TAH
Pulsatile
Intra
Long
Yes
BTT
Bilateral
(AbioMed) Abiocor TAH
Pulsatile
Intra
Long
Investigational
BTT
Bilateral
BTD, bridge to decision; BTR, bridge to recovery; BTT, bridge to transplantation; DT, destination therapy; Extra, extracorporeal; Intra, intracorporeal; L, left; Para, paracorporeal; Perc, percutaneously placed; PVAD, paracorporeal ventricular assist device; R, right; TAH, total artificial heart. a Federal Drug Administration approval status. b Indicated for paediatric population.
device with greatest durability and lowest incidence of adverse events and that provides satisfactory cardiac output for either one or both failing ventricles.
TRENDS IN LEFT VENTRICULAR ASSIST DEVICE USE AND OUTCOMES The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is the largest registry of MCS device utilization, with 145 participating hospitals. The most recent fifth INTERMACS annual report presents MCS data from 23 June 2006 to 30 June 2012. Durable MCS devices were used in 6885 patients, with 243 having a previous MCS device, 72 being paediatric patients and nine having an isolated right ventricular assist device (RVAD) [10]. Of the 6561 patients with primary implant for left ventricular support, 136 received a TAH, 910 received a pulsatile flow LVAD (68.1% LVAD only) and the remaining 5515 received a continuous flow LVAD (97.3% LVAD only) for BTT or destination therapy. Survival for all comers with a continuous flow LVAD was 80% at 1 year and 70% at 2 years. Furthermore, Park et al. [4] report similar 1-year survival rates with the exclusive use of HM II for destination therapy at 73% along with a significant reduction in haemorrhagic stroke-related deaths.
Prior to 2011, the majority of patients were listed as either BTT (patient currently listed for heart transplantation) or bridge to transplant candidacy/eligibility (likely BTT) with 65.4%, while destination therapy accounted for only 18.4% [10]. These trends have dramatically changed, starting in 2010 when the HM II was FDA approved for destination therapy. Thus, in 2011, BTT strategy dropped to 45% whereas destination therapy increased to 38.9% [10]. These trends continue into mid-2012, with BTT accounting for 42.8% and destination therapy accounting for 44% [10]. Moreover, indication for bridge to transplant candidacy or eligibility, which consists of sustained ventricular support in hopes of altering modifiable contraindications (i.e. renal dysfunction, high body mass index and pulmonary hypertension), has remained steady for LVAD indication at 24% [10]. With the advancement of LVAD technology, perioperative care and patient selection, these trends will likely continue and perhaps the number of patients for bridge to candidacy will increase, as the number of heart failure patients is increasing with a stagnant heart donor pool. In the INTERMACS report, freedom from device exchange or death related to device malfunction was similar for pulsatile and continuous flow devices for the first 8 months (96%); however, a significant linear decrease in the freedom from device
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malfunction in the pulsatile device group was seen after 8 months until 24 months (40%, P < 0.0001) as compared with the relatively steady freedom of device issue at 24 months in the continuous flow LVAD (94%) [10]. Furthermore, on the basis of competing outcomes (cardiac transplantation, death survival on MCS device and recovery) in another contemporary report, patients receiving pulsatile flow LVADs were less likely to be alive at 12 months (31%) when compared with continuous flow LVADs at 12 months (54%) [11]. In addition to improved survival, quality of life, general well being and ability to perform self-care significantly improved and remained steady out to 12 months post-LVAD implantation [4,10]. Albeit a small retrospective survey study, sexual function overall was reported worse at 12 months postcontinuous flow LVAD implant, which may be attributed more to psychological issues such as fear of damaging the device and self/partner harm [12]. Finally, although the left ventricle is typically intact, the term LVAD is a relative misnomer, as most devices are being implanted to physiologically replace the function of the left heart (i.e. left heart replacement).
LEFT VENTRICULAR ASSIST DEVICE COMPLICATIONS When considering MCS versus heart transplantation for heart failure therapy, one needs to evaluate the complications associated with each strategy: MCS therapy complications include stroke, bleeding, infection and device malfunction, while heart transplantation complications include rejection, infection, malignancy and allograft vasculopathy. Although survival free of stroke is high at 12 and 24 months with MCS, the actuarial freedom from any major adverse event including infection, bleeding, device malfunction, stroke or death is quite low, with 30% at 12 months and 19% at 24 months irrespective of age and INTERMACS level (see Table 2) [10,13,14]. Rate of device failure over time
represents the MCS engineering measure of durability, which can result from either a mechanical issue (motor failure) or a biological one (device thrombosis or haemolysis). Pump failure may lead to significant clinical outcomes including death, stroke, bleeding, infection and redo-surgery for pump exchange, which in a recent study was shown to afflict 17% of patients requiring pump change for device failure [15]. Furthermore, readmission rates for continuous flow LVAD patients remain high at 1.64 1.97 admissions per patient-year follow up [16 ]. A recent prospective multicentre study [17] reported that 22% of HM II patients had an infection, with the driveline site being the most common and Staphylococci being the most common pathogen (47%), and that a history of depression and elevated serum creatinine were independent predictors of device infection. Alternatively, the most common reason for readmission is due to bleeding, mainly from the gastrointestinal tract [16 ]. It has been hypothesized that continuous flow devices (HM II or HeartWare HVAD), with low or nonpulsatile flow characteristics, replicate the mechanism of aortic stenosis. This leads to colonic mucosal ischaemia along with high shear stress, resulting in acquired von Willebrands disease, arteriovenous malformations and thus gastrointestinal bleeding [5,18–20]. Although acquired von Willebrands dysfunction may be a likely contributor to LVAD-related gastrointestinal bleeding, the true mechanism is likely multifactorial, with oral anticoagulation use, age and previous history of gastrointestinal bleeding being a few known risk factors [19,21]. Nevertheless, when comparing adverse events between pulsatile and continuous flow MCS devices, it is quite evident that pulsatile devices have increased rates of adverse events in all categories. Specifically, the rate for device malfunction expressed as events per 100 patient-months is 3.26 in the pulsatile group compared with 1.60 in the continuous group (P < 0.0001). Also, bleeding and infection rates are significantly higher in the &&
&&
Table 2. INTERMACS clinical profile levels INTERMACS level
Title
Clinical description
1
Cardiogenic shock
Life-threatening hypotension with escalating inotropic and vasopressor support
2
Progressive decline
Despite inotropic support still demonstrates continued deterioration
3
Stable with inotropes
Stable on moderate inotropic support or temporary mechanical circulatory support
4
Resting symptoms
Patient at home on optimal medical therapy but frequently has NYHA IV symptoms
5
Exertion intolerant
Patient comfortable at rest but unable to engage in any activity
6
Exertion limited
Patient comfortable at rest and able to do very mild activity
7
Advanced NYHA III
Despite history of previous decompensation, patient comfortable at mild activity
NYHA, New York Heart Association. Adapted with permission [13,14].
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pulsatile group (17.28 and 22.81, respectively) versus the continuous group (9.45 and 8.01, respectively; P < 0.0001) [10]. Thus, it is no wonder that, as of 2009 and onwards, more than 85% of all implanted devices for BTT or destination therapy were continuous flow MCS devices. Moreover, from 2010 onwards, nearly 100% of patients for destination therapy received continuous flow LVADs [10].
blood via an outflow arterial cannula. Although survival rates utilizing ECMO in refractory cardiogenic shock patients vary regarding clinical indication, with survival to discharge ranging from 39 to 80% [23,24], the lack of durability (limited to days, with mean of 3.8 days) and the bleeding/coagulopathic issues surrounding vascular access are major shortcomings of this intervention [23,25,26].
LEFT VENTRICULAR ASSIST DEVICE SELECTION
Extracorporeal mechanical circulatory support
After patient selection and optimization are achieved, MCS device selection should then be tailored according to patient’s expectations and general clinical status and upon recommendations from a multidisciplinary approach. Patients who are haemodynamically stable or classified as INTERMACS 3 or greater can be considered for BTT or destination therapy. In both instances, a durable, long-term MCS device such as the HM II, HeartWare HVAD or Abiomed AB5000 is the device of choice (Table 2). If the patient is haemodynamically unstable or progressively declining (INTERMACS 1 or 2), short-term MCS therapy should be immediately considered (Table 2). This buys the heart failure team time to make a decision for further management [bridge to decision (BTD)] or can provide the patient with essential circulatory support for myocardial recovery.
Some of the older extracorporeal MCS devices used include the Abiomed BVS5000 (Abiomed Inc., Danvers, Massachusetts, USA), a nondurable pulsatile pneumatically driven device, the Abiomed AB5000, and the Thoratec Paracorporeal Ventricular Assist Device II. More recently, the Levitronix CentriMag (Levitronix LLC/Thoratec Inc., Waltham, Massachusetts, USA) (Fig. 1), a third-generation device that uses a magnetically levitated rotary pump designed for temporary extracorporeal support (flow rates up to 10 l/min), is used in patients with postcardiotomy shock, allograft failure, right ventricular failure with existing LVAD and refractory heart failure after acute myocardial infarction. Although the FDA has approved CentriMag for providing temporary right ventricular support after LVAD insertion for up to 30 days, several studies have used the CentriMag for more than 100 days with no increased incidence of thromboembolic complications [27]. Loforte et al. [28] describe their 1 and 2-year survival results with this device in 42 patients with the majority in postcardiotomy shock or right ventricular failure after LVAD placement (55 and 24%, respectively). This approach created a BTD by temporarily establishing adequate systemic perfusion and altering the patient’s INTERMACS profile (Table 2) [29].
SHORT-TERM LEFT VENTRICULAR ASSIST DEVICE OR RIGHT VENTRICULAR ASSIST DEVICE OPTIONS: INTRA-AORTIC BALLOON PUMP Intra-aortic balloon pump (IABP) is commonly used as the first mechanical support treatment in efforts to improve coronary perfusion in the setting of refractory cardiogenic shock. Although some patients may benefit from IABP versus other forms of MCS, a recent randomized controlled trial comparing IABP with controls (best medical therapy) demonstrated similar 30-day mortality and major adverse events [22]. Thus, more research is needed to determine in which clinical setting it would be advantageous to use IABP.
Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation (ECMO) is a rapid, easy to initiate mode of emergency biventricular support. This system provides excellent haemodynamic support via a nonpulsatile pump, membrane oxygenator that receives blood via inflow venous cannulas and returns oxygenated
Percutaneous mechanical circulatory support With the advancement of MCS technology, percutaneous insertion of LVADs can be achieved with devices such as the Impella LP (Abiomed) (Fig. 1) and the TandemHeart (CardiacAssist, Pittsburgh, Pennsylvania, USA). Although the main indication for utilization of percutaneous LVADs is for highrisk percutaneous coronary intervention, these miniaturized LVADs have been used to provide adequate perfusion (2.5–5 l/min) in some patients with acute transient haemodynamic instability such as myocarditis, or allograft rejection. Cardiogenic shock may result from biventricular failure, thereby increasing the demand for RVAD. After haemodynamic stability is achieved via nondurable MCS therapy, clinicians must continuously evaluate and
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consider weaning from this short-term strategy or proceeding to long-term MCS. Impella devices are approved for up to 7 days; however, some centres maintain patients on Impella support for up to 27 days (mean ¼ 14.2 days) by means of a right axillary approach [30–32]. Although guidelines are still being updated, it is common practice to reduce the MCS flows by 0.5 l/min and assess the following: clinical status, native left ventricular contraction, ancillary blood work (lactate) and echocardiography [33].
LVAD technology, surgical methods and postoperative management: Goldstein et al. [39] present an in-depth algorithm for diagnosing and treating LVAD thrombosis, a serious complication following LVAD insertion. Lastly, mounting evidence suggests that allowing the native aortic valve to open at least 50% of the time (achieving a pulse pressure >15 mmHg) may minimize the incidence of de-novo aortic insufficiency [40–42] likely due to commissural fusion of the valve leaflets [43].
CONCLUSION FUTURE CONCEPTS The HeartWare miniaturized VAD is a new, smaller continuous axial flow pump, with the same magnetically driven ‘contactless’ impeller, that will likely begin clinical trials in 2013. Along with this ultraminiature design (available as RVAD), this company is researching the use of transcutaneous energy transfer technology in efforts to discontinue the need for a driveline-mediated energy source. Also, Thoratec Inc. is conducting research and development for a third-generation LVAD (HeartMate 3) that is ultracompact and magnetically levitated and has the ability to induce pulsatility. The CARMAT heart, a bovine bioprosthetic heart mimicking the heart’s ventricles, will begin clinical trials this year in medical centres across Europe and the Middle East. This TAH is unique, with a lined bovine pericardial tissue to reduce the incidence of clotting, and is embedded with microsensors to adjust blood flow in response to patients’ needs. Finally, miniaturized percutaneous pumps (Impella, TandemHeart) to assist either the left or the right ventricle may supplement current larger LVADs by providing 2–3.5 l/min of cardiac output. These devices have already been implanted via an axillary approach, allowing patient ambulation and return of normal functioning [31]. Also, the SYNERGY (CircuLite Inc., Teaneck, New Jersey, USA) micropump surgical system providing 4.25 l/min of flow has received FDA conditional approval to undergo a feasibility trial enrolling patients in INTERMACs level of at least 4 (Table 2). Management guidelines for LVAD patients are continually being updated, with more centres reporting their results [10,34,35]. Some relative contraindications to LVAD insertion include acute cardiogenic shock with uncertain neurological status, active severe bleeding, active uncontrolled systemic infection, severe right ventricular dysfunction, severe aortic insufficiency that will not be corrected or mechanical aortic valve that will not be converted to a bioprosthesis [35–38]. These contraindications will change with improvement in 172
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It is clear that to achieve better outcomes for our patients with significant heart failure, a mechanical condition, we need to utilize a mechanical intervention. Heart transplantation is the gold standard and provides exceptional long-term results, but is limited based on the stagnant donor pool and the increasing complexity of patient comorbidities, thereby leading to heart transplantation contraindications. There has been dramatic advancement of durability found in the second and third-generation, continuous flow LVADs, along with improved survival rates in patients receiving these devices for destination therapy. MCS may soon become the treatment option of choice in refractory heart failure patients, especially with further evolution of less invasive approaches, smaller designs, and energy sources. Acknowledgements None. Conflicts of interest M.R. received research support and honoraria from Medtronic Inc.
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Mechanical support for heart failure therapy Toeg et al. 6. Morshuis M, El-Banayosy A, Arusoglu L, et al. European experience of DuraHeart magnetically levitated centrifugal left ventricular assist system. Eur J Cardiothorac Surg 2009; 35:1020–1027; discussion 1027–1028. 7. Copeland JG, Smith RG, Arabia FA, et al. Cardiac replacement with a total artificial heart as a bridge to transplantation. N Engl J Med 2004; 351:859– 867. 8. Slepian MJ, Alemu Y, Girdhar G, et al. The Syncardia total artificial heart: in && vivo, in vitro, and computational modeling studies. J Biomechanics 2013; 46:266–275. An important article that describes the most recent trends in MCS therapy. 9. Kirsch ME, Nguyen A, Mastroianni C, et al. SynCardia temporary total artificial heart as bridge to transplantation: current results at la pitie hospital. Ann Thorac Surg 2013; 95:1640–1646. 10. Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6000 mechanical circulatory support patients. J Heart Lung Transplant 2013; 32:141–156. 11. Holman WL, Naftel DC, Eckert CE, et al. Durability of left ventricular assist devices: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 2006 to 2011. J Thorac Cardiovasc Surg 2013; 146:437– 441. 12. Eckman P, Dhungel V, Mandras S, et al. Sexual function after left ventricular assist device. J Am Coll Cardiol 2013; 61:2021–2022. 13. Barge-Caballero E, Paniagua-Martin MJ, Marzoa-Rivas R, et al. Usefulness of the INTERMACS Scale for predicting outcomes after urgent heart transplantation. Rev Esp Cardiol 2011; 64:193–200. 14. Kirklin JK, Naftel DC, Kormos RL, et al. The Fourth INTERMACS Annual Report: 4000 implants and counting. J Heart Lung Transplant 2012; 31:117– 126. 15. Stephenson E, El-Banayosy A, Soleimani B. Incidence of pump failure and change in continuous flow left ventricular assist devices [Abstract]. 93rd AATS meeting, Minneapolis, MN, US, 7 May 2013. 16. 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. A useful study reporting the incidence and cause of MCS infections and common ways to treat or prevent these complications. 17. Gordon RJ, Weinberg AD, Pagani FD, et al. Prospective, multicenter study of ventricular assist device infections. Circulation 2013; 127:691–702. 18. Uriel N, Pak SW, Jorde UP, et al. Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J Am Coll Cardiol 2010; 56:1207–1213. 19. Klovaite J, Gustafsson F, Mortensen SA, et al. Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). J Am Coll Cardiol 2009; 53:2162–2167. 20. Demirozu ZT, Radovancevic R, Hochman LF, et al. Arteriovenous malformation and gastrointestinal bleeding in patients with the HeartMate II left ventricular assist device. J Heart Lung Transplant 2011; 30:849–853. 21. Muthiah K, Robson D, Macdonald PS, et al. Increased incidence of angiodysplasia of the gastrointestinal tract and bleeding in patients with continuous flow left ventricular assist devices (LVADs). Int J Artif Organs 2013; 36:449– 454. 22. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012; 367: 1287–1296. 23. Paden ML, Conrad SA, Rycus PT, et al. Extracorporeal Life Support Organization Registry Report 2012. ASAIO J 2013; 59:202–210. 24. Prodhan P, Bhutta AT, Gossett JM, et al. Comparative effects of ventricular assist device and extracorporeal membrane oxygenation on renal function in pediatric heart failure. Ann Thorac Surg 2013; 96:1428–1434.
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