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Editorial

Mechanical Circulatory Supportfor the Failing Heart: Past, Present

and FutureDonald Esmore, AO, FRACS and Franklin L. Rosenfeldt,

MD, FRACSCJOB Department of Cardiothoracic Surgery, Alfred Hospital, Baker Heart Institute andDepartment of Surgery, Monash University, P O Box 315, Prahran, Vic. 3181, Australia

Available online 26 July 2005

Heart failure accounts each year for approximately2500 deaths in Australia and 250,000 in the USA, de-

spite significant advances in medical therapy over the lastdecade. The 50% 1-year mortality for advanced heart fail-ure is greater than for most malignancies. With the popu-leoi

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ular assist devices assist either the left ventricle, the rightventricle or less commonly both ventricles.A window of opportunity for mechanical circulatory

support devices opened in 1984. With some 20% ofprospective transplant patients dying whilst on the wait-

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ation ageing, the number of patients in their seventh andighth decades continues to rise and heart failure as withbesity, is predicted to reach pandemic proportions earlyn this millennium.In 1963 DeBakey was the first to successfully treat heart

ailure with a mechanical circulatory support device af-er cardiac surgery. Progress, however, was slow duringhe 1970s with isolated case reports documenting limiteduccessful clinical device usage. A groundswell of opti-ism that mechanical replacement for the failing heartas possible, culminated in the implantation of a total ar-ificial heart, the Jarvik-7, in December 1982 in Utah, USA.he initial optimismwas short-lived asmultiple complica-ions ensued and the patient died, after 4 morbidity-filledonths. The media was scathing, describing the implants, “a clinical experiment, an indictment of the medicalrofession”. Nevertheless four further implants followedn Audibon, Kentucky. Less than acceptable results sawhe Jarvik-7 and subsequently the Symbion, total artificialeart eventually deregistered by the US Food and Drug

ing list, the idea of temporarily supporting these patientswith amechanical device until a donor heart becameavail-able was very appealing. And so “bridge to cardiac trans-plantation” became a clinical reality thus supporting thestruggling domain of mechanical circulatory support. Ini-tial success with the Novacor and Thoratec devices led tothe development of other devices, collectively achievingsuccessful temporary support for an otherwise doomedpopulation. Periods of reliable cardiac support formonths,discharge to home care and a general increased level ofunderstanding of the patient-device interface establishedmechanical circulatory support as a relevant and valuabletherapy.

Types of Cardiac Assist Devices

The 30 or more devices currently in use or developmentcan be divided into blood pumps and counterpulsationdevices. Blood pumps can be either pulsatile or non-

dministration due to poor performance and attendantorbidity.

pulsatile. Pulsatile, or positive displacement (first gen-eration) devices, contain valves and mimic the pulsatilenature of the native circulation. Commercially availableptvltutpttEt

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It had become clear that completely replacing the heartith an artificial device was not be the best way forward.entricular assist devices (VADs) that support but do noteplace the failing heart had been utilised increasingly af-er open heart surgery since the early 1970s and were con-idered by many in the field as a more promising optionhan cardiac replacement in treating advanced heart fail-re. Implantation required a less demanding surgical pro-edure and retained the native heart as a back-up. Ventric-

Corresponding author. Tel.: +61 3 9276 3684; fax: +61 3 9276 2317.-mail address: f.rosenfeldt@alfred.org.au (F.L. Rosenfeldt).

2005 Australasian Society of Cardiac and Thoracic Surgeustralia and New Zealand. Published by Elsevier Inc. Al

ulsatile ventricular assist devices include the Thoratec,he Novacor and the HeartMate-VE. Non-pulsatile de-ices are either centrifugal pumps or axial flow (turbine-ike) pumps. These are smaller, simpler and less expensivehan the pulsatile devices. The downside to these contin-ous flow devices is that they may cause haemolysis, mayhrombose, or their bearings may fail. Collectively, non-ulsatile devices have experienced only a limited time inheclinical arenaandpredominantly in thebridgeapplica-ion, i.e. short termsupport before cardiac transplantation.xamples of non-pulsatile (second generation) pumps ofhe axial type include, the Jarvik 2000, theDeBakey and the

and the Cardiac Society ofts reserved.

1443-9506/04/$30.00doi:10.1016/j.hlc.2005.03.019

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164 Esmore and Rosenfeldt Heart Lung and CirculationMechanical circulatory support for the failing heart 2005;14:163–166

HeartMate II pumps and the third generation axial flowdevices, the Incor, and the centrifugal flow VentrAssist,Coraide and Duraheart VADs.Counterpulsation devices aim to synchronously com-

press the aorta and thereby improve cardiac output andcoronary blood flow.1 The C Pulse extra-aortic counter-pulsation device reported for the first time in the articleby Davies et al. in this issue is one such device. The advan-tages of counterpulsation devices are that they are simple,have fewmoving parts and are not life-threatening if theyfail. Theirmain disadvantage is that they can augment car-diac output only by 1.0–1.5 L/min.Mechanical support may be either temporary or per-

manent. Temporary support or “bridging” is most com-monly used as a prelude to transplantation and accountsfor approximately 2000 implants per annum world wide.Rarely, the heart may recover and the device can be re-moved, “bridge to recovery”. Permanent support, knownas “destination therapy” assists the heart for the remain-der of the patient’s life. This has become a more realisticoption as the results of long-termbridginghave improved.

Role of Heart Transplantation

Cardiac transplantation remains the most effective andreliable form of treatment for advanced heart failureunresponsive to medical therapy in patients aged less

the heart failure population, the heart recovers dramati-cally during circulatory support enabling the device to beexplanted. Various strategies have been tried during me-chanical cardiac circulatory support to encourage recoveryand reverse the remodelling of the heart. The use of phar-macological agents such as clenbuterol combined with aconventional heart failure treatment regimen3 or apher-sis to remove harmful cytokines and neurohormones havebeen tried with various degrees of success.4

Destination therapy is the application of circulatory as-sistance where the greatest need resides for the worldheart failure population. The landmark FDA-approvedREMATCH Trial, published in November 2001, was aprospective randomised trial of mechanical support usingthe Heartmate I-VE compared to optimal medical man-agement in a population of advancedheart failure patientswho were not transplant candidates.5 The 2-year survivalin the mechanical support group was 23% compared to8% in the medical group. There was a 35% device failureat 2 years, as a consequence inherent design problems.Results, however, confirmed a survival and quality of lifebenefit for the mechanical support group prompting theFDA in 2002, to approve theHeartMate-VE device for des-tination therapy at selected centres.

The VentrAssist Left Ventricular Assist System

than 65 years. However, despite the increasing preva-lence of heart failure, the usage of heart transplantationworldwide is actually decreasing (a 31% decrease from1994 to 2002).2 This is largely due to a shortage of suitabledonors but also due to the improved results of medicaltherapy for advanced heart failure. This worseningsupply/demand imbalance for donor hearts remains thestimulus for research and development of artificial heartsand ventricular assist devices.

Current Status of Mechanical Cardiac Support

Total artificial heart technology is still in use today but dueto poor long-term results its application is limited to a fewcentres worldwide. Total artificial hearts are complicated,large, expensive and ultimately unreliable as permanentlife-support systems. The original Jarvik-7 device, how-ever, survives to this day as the CardioWest Total ArtificialHeart with selected centres achieving excellent results inthe bridge to transplant application.LVADs are the most commonly used form of mechani-

cal cardiac support, mainly as a bridge to transplantation.The results ofmechanical support as a bridge to transplan-tation are extremely good with most patients being sup-ported for 3–6 months before heart transplantation withan overall post-transplant survival comparable to ortho-topic heart transplantation, namely 50% 10-year survivaland 30% 15-year survival.2

Bridge to recovery (less than 10% of all implants) isachievable in patients with potentially reversible formsof cardiomyopathy such as viral myocarditis, and post-partum cardiomyopathy. However, even in some cases ofidiopathic dilated cardiomyopathy, a large component of

The VentrAssist left ventricular assist system (LVAS) isan Australian invention designed to assist the failingheart on a temporary or permanent basis. Initially con-ceived in 1999, the VentrAssist is currently in an advancedstage of clinical evaluation and shows great promise. TheVentrAssist is a third generation device with a unique,hydrodynamically-suspended, bearingless rotor with lowthrombogenicity and minimal anticoagulation require-ments (Fig. 1). Following implant evaluation in 50 sheepwithout anticoagulation, supported for up to 6 monthsand with a cumulative support time of 7.2 years,6 thePhase 1 (safety and efficacy evaluation) human implantprogram was commenced at The Alfred Hospital in June2003. Nine patients in NYHA Class IV heart failure wereimplanted. The majority were elderly with multiple co-morbidities, having exhausted all other management op-tions. The first patient survived 19 months, lived at homeand died of iatrogenic renal failure.7 Two other destina-tion therapy patients are currently well and at home at 7and 15months post-implant. One patientwas successfullybridged to transplantation after 4 months of support. Thefive other patients, predominantly implanted as a bridgeto transplantation, succumbed to causes not directly re-lated to the device.The program has now moved on to the Phase II trial

including approximately 35 patients mainly implanted asbridge to transplantation. Seven further implants havealready been performed in Australia, two as destinationtherapy and five as a bridge to transplantation. Future im-plants are approved for the UK, Norway and more re-cently the USA. This device has a particular advantagefor the destination therapy patient, with its silent func-tion, small size, low rates of infection and thrombosis

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Heart Lung and Circulation Esmore and Rosenfeldt 1652005;14:163–166 Mechanical circulatory support for the failing heart

Figure 1. The VentrAssist ventricular assist device.

and with a theoretically long life, thus providing excel-lent quality of life for the patient with advanced heartfailure.

The C Pulse Extra-aortic Counterpulsation Device

This device was invented by Dr William Peters, a NewZealander who trained in cardiac surgery in Australia be-fore establishing the Sunshine Heart Company in Syd-ney. Dr Peters was also responsible for another medicalinvention, a systemforpercutaneouscardiopulmonaryby-pass and cardioplegia for use in minimally invasive car-diac surgery. In fact Dr Peters published the first accountof this technology also in Heart Lung and Circulation 1993;2:152–154 (The Australasian Journal of Cardiac and Tho-racic Surgery as it then was). This technology was furtherdevelopedby theHeartPortCompany inCaliforniaachiev-ing limitedusagearound theworldasapractical techniquefor minimally invasive cardiac surgery.The current report by Davies et al. (Heart Lung Circ

2005;14:178–186) describes the use of the C Pulse in pigsand compares its haemodynamic effects with those of anintra-aortic balloon pump (IABP). The authors concludethat the C Pulse is at least as effective as IABP counterpul-sation and has the advantage of being able to be used ona permanent basis and avoiding complications due to in-sertion of the IABP through the femoral artery. However,ihdu

failure and no cardiac output measurements were made.Nevertheless the efficacy of the device was well demon-strated.Subsequently the authors have implanted 26 sheepwith

the C Pulse with survival for as long as 10 months. The re-sults showed a high degree of safety and reliability and noserious aortic damage. The investigators then went on toplace the device temporarily around the aorta in six pa-tients undergoing off-pump cardiac surgery in a clinicalfeasibility study at Green Lane Hospital in New Zealand.The results showed 20ml blood volume displacement perbeat at 76 beats/min (equating with an augmentation ofcardiacoutputof 1.5 L/min), and improvements in left ven-tricular function due to the systolic unloading. No embolior other complications were seen in this acute study (un-published data). The investigators now propose a Phase Iclinical trial where the device will be implanted into up to20 patients with NYHAClass III heart failure. If the devicethen proves efficacious and safe, a Phase II randomisedstudy is planned.

Conclusion

Cardiac transplantation is the gold standard for cardiac re-placement and will remain so for the forseeable future. Itis unchallenged in providing NYHAClass I survival with-out the attendant morbidity that remains the tyranny ofitpfmk

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t is not clear from this study whether the C Pulse has anyaemodynamic advantage over the IABP because of theesign of the experiments where the C Pulse was alwayssed prior to the IABP. Also, the pigs were not in heart

mplanted mechanical devices, and the need for tetheringo an external power source. With only 3500 cardiac trans-lants performed annually worldwide, and with numbersalling (ISHLTx Annual Report, 2004) transplantation re-ains a scarce resource in an expandingheart failuremar-et.Mechanical circulatory support iswell established in theridge to transplant applications, having achieved goodesults with up to 70% of implants being successfullyridged in the majority of published series. Permanentechanical circulatory support, however, poses greaterroblems, given the serious adverse event profiles of cur-ent devices, the morbidity from infection, the need fornticoagulation, compounded by the inherent lifelong de-endence on a mechanical device. Design advantages ofhe VentrAssist–LVAS and C Pulse may overcome some ofhese problems, with the potential to play a pivotal role inhis emerging area of servicing the expanding and ‘grey-ng’ heart failure population.As clinical experience builds and devices improve, des-

ination therapy may become available on a wider scaleo the terminal heart failure population for whom heartransplantation is not an option due to advanced age or co-orbidities. Timewill tell if destination therapy, describedy Yacoub as “a fantasy of the 20th century” will becomea miracle of modern medicine” in the 21st century, a sta-us achieved by modern era cardiac transplantation onlyn the last decade of the preceding century.

isclosure

. Esmore is a salaried consultant for Ventracor Inc.

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References

1. Jeevandam V, Jayakar D, Anderson AS, et al. Circulatory as-sistance with a permanent implantable IABP: initial humanexperience. Circulation 2002;106(12 Suppl. 1):I183–8.

2. International Society for Heart and Lung Transplantation Reg-istry. J Heart Lung Transplant 2004;23:796–803.

3. Yacoub MH. A novel strategy to maximise the efficacy of leftventricular assist devices as a bridge to recovery. Eur Heart J2001;22:534.

4. Entwistle 3rd JW. Short and long-term mechanical ventricu-lar assistance towards myocardial recovery. Surg Clin North Am2004;84:201–21.

5. RoseEA,GelijnsAC,MoskowitzAJ,HeitjanDF, StevensonLW,Dembitsky W, et al. Long-term use of a left ventricular assistdevice for end-stage heart failure.NEngl JMed 2001;20:1435–43.

6. Van der Meer A, James NL, Edwards GA, Esmore DS, Rosen-feldt FL, Begg JD, et al. Initial in vivo experience of the Ven-trAssist implantable rotary blood pump in sheep. Artificial Or-gans 2003;27:21–6.

7. Esmore DS, Kaye D, Salamonsen R, Buckland M, Rowland M,Negri J, et al. First clinical implant of the VentrAssist left ven-tricular assist systemasdestination therapy for end-stageheartfailure. J Heart Lung Transplant, in press.