chapter 95 · chapter 95 future directions in cardiac surgery o.p. yadava † kundu currently less...

791

Chapter 95 Future Directions in Cardiac Surgery O.P. YADAVA • A. KUNDU

currently less than 10% of CABGs in India 6 . Future endeavours will thus be on maximizing the use of arterial grafts, regardless of the technique used (off- or on-pump), a point prophetically made by the mastermind of the ART trial, Taggart himself 7 .

HYBRID REVASCULARIZATION 8

This technique was devised to provide the patient the best of both worlds namely, the superior long-term survival benefi t of a surgical left internal mam-mary artery (LIMA) to left anterior descending artery (LAD) graft, and the less invasive percutaneous in-tervention (PCI) to the non-LAD vessels. In keeping with the philosophy of ‘noninvasiveness’, the LIMA-LAD is performed by minimally invasive or robotic means, thereby avoiding a median sternotomy.

Despite the obvious patient benefi ts, hybrid re-vascularization has not gained traction due to the lack of large-scale randomized controlled trials (RCTs) comparing it with pure CABG or multivessel PCI which will need to be addressed in the near future. We also have no data comparing hybrid pro-cedures with CABG, especially in the era of fourth-generation drug-eluting stents. The next decade or so should see these aspects being examined with a view to establishing hybrid revascularization as a standard procedure in treating CAD.

ROBOTIC AND MINIMALLY INVASIVE CABG

‘One size fi t all’ CABG is a paradigm of past. In the future, we are going to see more customized opera-tions, which are meant to fi t the needs of an indi-vidual. More and more patients will receive endo-scopic procedures through techniques such as minimally invasive direct coronary artery bypass

Cardiac surgery has taken great strides ever since Ludwig Rehn performed the world’s fi rst successful heart operation when he repaired a stab wound suf-fered by a gardener over a century ago. The obvious diffi culty of operating on the heart hampered the development of the fi eld, and cardiac surgery had to await the development of the heart–lung machine (cardiopulmonary bypass, CPB) by Gibbon in 1953. Thereafter, it was steady progress, albeit marked by numerous failures, setbacks, ego clashes and lost patients. As the specialty grew with all its complexi-ties, subspecialties like coronary, valvular, paediatric/congenital and of course minimal access surgery took shape. Future directions would perforce have to be bundled into these respective divisions in order to get a better perspective.

CORONARY ARTERY DISEASE

CORONARY ARTERY BYPASS SURGERY

Based on the SYNTAX and FREEDOM trials, it has been long-established that coronary artery bypass grafting (CABG) remains the gold standard treat-ment in terms of survival and freedom from myo-cardial infarction (MI) and the need for repeat revas-cularization. A raging controversy is the off-pump (OPCAB) versus on-pump debate. No study has managed to conclusively prove the superiority of one over the other. The most recent are the CORO-NARY 1 and the GOPCAB 2 trials. Both found no signifi cant differences in composite outcomes at 30 days and 1 year by either of the modalities and it is probably the surgeon, rather than the technique that is the bone of contention 3 .

Despite the compelling evidence for the use of multiple arterial grafts as a ‘MultiArt’ strategy 4 , 5 , bilateral internal mammary artery (IMA) usage is

792 SECTION XI — Cardiac Surgery

(MIDCAB), minimally invasive multivessel coro-nary artery surgery (MICAS) or total endoscopic coronary artery bypass (TECAB). Although results have been excellent 9 in the hands of a limited few, a clear benefi t to the robotic approach, though not yet demonstrated, is expected in the future along with its wider dissemination.

ANASTOMOTIC DEVICES

The emergence of MICAS/robotic coronary surgery has led to the development of automated coronary anastomotic devices 10 . These devices use various mechanisms to achieve a sutureless anastomosis, like Nitinol clips and pins (e.g. U-clip, Distal Anas-tomotic Device), steel clips (C-port), magnetic coupling between the conduit and coronary artery (Ventrica) or automated delivery of a preset num-ber of sutures through conduit and coronary artery after aligning them in position (HeartFlo). Of these, only the U-clip and C-port are USFDA ap-proved, with the former having shown the most promising results with similar graft patency as with hand-sewn anastomoses. The role of these devices will only increase as MICAS becomes com-monplace. Coronary-conduit coupling devices and connectors too are being evaluated and may be-come available in future.

CONDUITS

Prevention of Vein Graft Failure

The patency of saphenous vein grafts (SVG) and the paucity of conduits in a population increas-ingly undergoing redo CABG is a problem. One potential game-changer, which could see increased use in future is the VGS (vein graft support) FLU-ENT device which covers the entire length of vein graft to protect it from kinks or bends 7 . The VEST II (Venous External Support Trial) was a follow-up to the original VEST which showed that use of the device, along with minor iterations, was associ-ated with improved SVG patency in the left sided system 11 .

Gene therapy is attractive as an ex vivo method to genetically manipulate the conduit before graft-ing. Smooth muscle cell proliferation is a key fea-ture of neointimal hyperplasia leading to vein graft failure. It was theorized that genetic inhibition of the transcription factor E2F could prevent smooth muscle cell proliferation 12 . Vein grafts treated with the E2F factor demonstrated mitigation of intimal hyperplasia and resistance to graft atherosclerosis in

the animal model 13 . Another approach being tried to improve graft patency is genetic ‘silencing’ of adhesion molecules that code for formation of ad-hesions and consequent stenosis in vein grafts 14 .

Future research will focus on identifi cation of new molecular targets involved in smooth muscle cell proliferation that could be targeted to enhance vein graft patency.

Alternative Conduits

The search for alternative conduits has led to use of human umbilical vein grafts and treated bovine IMA, but with limited success. 3D printing and tis-sue engineering are being evaluated to synthesize conduits which could be used off-the-shelf in the future. The challenges faced are daunting; these include providing an elastic vessel wall that can withstand cyclic loading, matching graft and host vessel compliance and, above all ensuring a non-thrombogenic intima 15 .

NO OPTION CAD-CORONARY VENOUS BYPASS GRAFTING

A group of patients with CAD have advanced dif-fuse disease with poor vessel runoff. These pa-tients may not be amenable to either CABG or PCI. Such patients may be offered a surgical op-tion based on arterialization of the cardiac venous system 16 . More recently, arterialization of the great and middle cardiac veins (parallel to the LAD and PDA, respectively) has been explored. Patients with nongraftable right coronary artery (RCA) dis-ease undergoing CABG were included in the trial. One group received an IMA graft to the middle cardiac vein, while the other group did not get any graft to the RCA territory. Three-month fol-low-up revealed no ischaemia/angina in the CVBG group along with increase in ejection fraction (EF), while a signifi cant number of patients in the nongrafted RCA group showed ischaemia in that territory 17 .

In view of the apprehension of myocardial oe-dema and haemorrhage from retrograde venous perfusion at arterial pressure, a fl ow-regulated SVG has also been used besides the autoregulating IMA. Future refi nements may even see the development of percutaneous techniques of creation of cardiac arteriovenous fi stula 18 between the coronary artery/left ventricle (LV) cavity and the accompanying vein, and this concept may offer a ray of hope in the future for patients rejected by the intervention-ist as well as the surgeon.

793Chapter 95 — Future Directions in Cardiac Surgery

ALTERNATE THERAPIES TO REVASCULARIZATION

Transmyocardial Laser Revascularization (TMLR)

TMLR has emerged as a USFDA-approved class IIB AHA indication for patients with intractable symp-toms due to diffuse disease not amenable to revascu-larization 19 . However, future research shall be cen-tred upon using TMLR along with adjuvant therapy in the form of stem cells to stimulate angiogenesis and myogenesis. Although haematopoietic stem cells, endothelial progenitor cells, mesenchymal stem cells (MSCs), myoblasts and undifferentiated side-population cells have been used clinically 20 , bone marrow stem cells have shown the most prom-ise. Future research will focus on the combination of these modalities for better functional outcomes 21 .

Stem Cell Therapies

Future advances in the therapeutic myocardial re-vascularization shall lie in the realm of molecular biology, with a view to improving tissue perfusion with the induction of vascular neogenesis, and pre-vention of vein graft atherosclerosis. Stem cell transplantation has emerged as a promising therapy for acute or chronic ischaemic cardiomyopathy. Multiple candidate cell types have been used in animal models and humans to repair or regenerate the injured heart including: embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), neo-natal cardiomyocytes, skeletal myoblasts (SKMs), endothelial progenitor cells, bone marrow mono-nuclear cells (BMMNCs), MSCs and, most recently, cardiac stem cells (CSCs) 22 . The clinical scenarios wherein these may be applied are

1. Acute MI with concomitant CABG: The aim of treating patients with stem cells after or during CABG following an episode of acute MI is to re-duce later remodelling, which is associated with adverse long-term prognosis 23 . The PRECISE (Per-cutaneous Robotically Enhanced Coronary Inter-vention) trial used adipose tissue–derived cells collected with lipoaspiration from patients at the time of CABG. These cells were subsequently re-infused into the endocardium of the LV postsur-gery by catheter. The fi nal results of this tech-nique are awaited 24 .

2. Refractory angina: Various cell types act as carri-ers of cytokines and growth factors in order to induce angiogenesis in the affected territory and thus relieve ischaemic symptoms 25 , 26 .

3. Chronic heart failure: Here the aim is to regener-ate areas of noncontractile myocardial fi brosis to achieve physiological and functional contractil-ity. The effects of such treatment on early post-operative rhythm abnormalities and LV remodel-ling will require further investigation 23 .

Recently, there has been interest in the study of transcription factors and signalling pathways in-volved in cardiac muscle regeneration following MI. This has led to the investigation of thymosin �4, which is a protein that can reactivate the cells’ embryonic developmental potential and stimulate epicardial cell transdifferentiation to vascular re-generation 27 . All of the above could represent po-tential future areas for intervention in conjunction with CABG in areas devoid of graftable coronary targets.

VALVULAR HEART DISEASE

Modifi cation in mechanical valve designs, with a view to improving their haemodynamics, by mak-ing the sewing ring small, increasing the effective orifi ce area, or by altering the shape and the angle of the disc, and even the number of discs, are being tried. Newer pivot mechanisms and nonthrombo-genic materials for reducing thromboembolism are likely to emerge. Therefore, a valve which is long-lasting and not requiring anticoagulation may not be a distant reality. Sewing rings impregnated with antibiotics to reduce infective endocarditis too are being currently evaluated.

Valve repairs have now become standard fi rst-line treatment options for patients with mitral re-gurgitation (MR), although this may not rigorously apply to rheumatic aetiologies. Reparative mitral valve (MV) surgery performed minimally has been found to have at least equivalent results to the con-ventional sternotomy approach and going forward these results can only improve 28 . Robotically as-sisted MV repair was documented to be safe by Paul et al. 29 . Complex MV procedures along with con-comitant problems can be tackled using the lateral endoscopic approach with robotics (LEAR) tech-nique as shown in the world’s largest series 30 .

In times to come, the success rate of MV proce-dures will be replicated even in the aortic valve (AoV) and repairs for bicuspid valves, besides tricus-pid valves, will become commonplace. The future buzzword would be to repair and respect native tis-sues with restoration of the normal 3D geometry of the aortic root, the functional aortic annulus and the LV.


OPTIONS FOR ISCHAEMIC MR

Quantitative Ventricular Restraint (QVR)

This concept arose out of a need for progressively increasing ventricular restraint following reverse re-modelling. The device consists of a fl exible, infl at-able, semi-ellipsoidal polyurethane balloon that fi ts around both ventricles. The balloon is connected to a one-way fl exible tubing in the subcutaneous plane in the chest wall, through which fl uid can be intro-duced into the balloon lumen. The volume of fl uid introduced is based on the intraluminal balloon pressure, which refl ects the epicardial pressure. Ani-mal studies showed an improvement in LV function at 3 weeks postimplantation 31 . Further studies will see if isolated LV restraint in the form of partial QVR can be more effective in isolated LV dysfunction and if it can obviate the need for opening the cardiac chambers on CPB to address is chaemic MR 32 . Off-shoots based on this concept are the VenTouch and BACE devices.

The VenTouch ( Fig. 95-1 ) is slipped around the LV via a small subcostal incision to provide gentle sup-port to the LV wall and minimize MR 33 . A subcuta-neously placed bladder connects to the fl uid-fi lled

chamber on the wrap that can be injected with sa-line on OPD basis, based on echocardiographic LV dimensions as well as epicardial pressure as men-tioned above. Its fi rst clinical implant was performed in 2014 and human trials are ongoing with prelimi-nary results expected later this year.

The BACE (basal annuloplasty of the cardia exter-nally, Fig. 95-2 ) is a strip of mesh with infl atable fl uid

BACE device schematic

SubcutaneousPorts

BarbFittings

Belt loops

Blunt NeedlePort

TensionBand

Fluid chambers

BACE device diagram

Implanted

Implanted

Figure 95-2. Intraoperative photo of BACE device showing postimplantation saline instillation (bottom right panel). From Hote, M., Seth, S., Choudhary, S. K., et al. Journal of the Practice of Cardiovascular Sciences, 2015;1:200–202.

Figure 95-1. The VenTouch device.


Secure assembly

Rapid valve preparation

Engineered to ensure only the correctsize valve and delivery system areconnected for procedural confidence.

No collapsing or foldingof the valve leafletsduring preparation orimplantation. Innovative balloon design

Incorporated within the delivery systemfor relible ballon positioning and inflation,as well as simplified device preparation.

Balloon expanded delivery for efficient procedures

The EDWARDS INTUITY Elite valve system utilizes threeguiding sutures in conjunction with the expanded frame forsecure annular placement, helping reduce procedural steps.

Figure 95-3. The Edwards Intuity device.

chambers implanted at the base of the heart, posi-tioned at the level of the atrioventricular groove and secured with sutures attached to the epicardium. It is designed to stabilize the MV annulus and to reduce the size or prevent further dilation of the basal myo-cardium. Here again, the infl atable fl uid chambers are connected by tubing to subcutaneous ports that re-main accessible postoperatively for future adjustment if needed 34 . These devices will provide a less invasive, future therapeutic option for ischaemic MR, without the attendant risks of major open heart surgery.

Transcatheter Procedures

Having shown effi cacy in prohibitive high-risk and intermediate-risk patients, transapical/femoral AoV replacement (TAVR) is likely to be approved even for low-risk patients with surgery reserved for a limited few. Paravalvular aortic leaks have already come down but complete heart block and the need for a permanent pacemaker need to be conquered. Trans-catheter MVR, wherein the valve is placed trans-septally, is on the horizon, with early feasibility tri-als having established the proof of the concept.

Anticoagulation

The future of postvalve surgery oral anticoagulation belongs to those drugs that provide effective and safe anticoagulation without the need for monitor-

ing. Drugs like oral factor Xa inhibitors (rivaroxa-ban, edoxaban), already approved for nonvalvular pathologies, will probably be approved for such patients. Until such a time, the future will see domiciliary international normalized ratio (INR) monitoring via kits like the Coaguchek, and tele-metric monitoring of prosthetic functions. These will enable early detection of prosthetic dysfunc-tion before it becomes life-threatening.

Sutureless Prostheses

The Perceval sutureless aortic prosthesis has been around for some years now and is emerging as a viable alternative in elderly frail patients. This is because it can be directly implanted via a small aortotomy using minimally invasive techniques, thereby considerably reducing the cross-clamp and CPB times 35 . Another ‘partially sutureless’ valve, the Edwards Intuity device ( Fig. 95-3 ), uses three marking sutures on a balloon-expandable stent and has been claimed to also signifi -cantly reduce the implantation time and aortotomy size, as well as provide good LV regression 36 . As costs come down, these valves will be used in more num-bers in even intermediate to low-risk patients in future.

‘Dry Packaged’ Bioprostheses

Bioprostheses are packed in a glutaraldehyde bath to eliminate antigenicity and act as a preservative.


However, a novel patent by Edwards has shown the way to a dry packaging of the prosthesis as glutaral-dehyde is known to be associated with an increased incidence of calcifi c degeneration, hence the man-datory ‘washing’ in normal saline prior to implan-tation. This ‘dry valve’ would provide a longer lifespan than that of current bioprostheses, which would enable its use in a younger population, with-out the risks of anticoagulation.

Tissue-Engineered Valves

Efforts are focused on creating tissue-engineered valves to address the twin problems of limited lifes-pan of bioprostheses, as well as the absence of small-sized valves for children, which would undergo so-matic growth with them. Tissue engineering is based on the concept that a scaffold of similar geometry to the natural valve is seeded with autologous cells harvested from the patient and cultured in static conditions, followed by in vitro cell conditioning or in vivo implantation ( Fig. 95-4 ). Such a scaffold can be created by one of the following two methods:

(a) The decellularization technique: This technique creates a natural extracellular matrix (ECM) in the shape of the valve. It has prompted concerns about immunologic and rejection reactions, be-cause despite a thorough decellularization, anti-genic proteins remain in the scaffold.

(b) The polymeric scaffold technique: This is based on the use of a scaffold made from synthetic

polymer alone (or in combination with natural materials). The design should mimic natural valve dynamics and, as the scaffold degrades, should assume the functionality of the valve 37 , 38 . The degree of degradation of the scaffold is criti-cal and must match the rate of tissue ingrowth, so that the valve grows with the child. Determin-ing this cross-point is critical to ensure that the tissue growth is suffi cient to take up the func-tionality of the valve before the scaffold com-pletely degrades 39 .

There are various synthetic biodegradable and nonbiodegradable polymers that can be used as scaf-fold for tissue-engineering, such as polyglycolide (PGA), polycaprolactone (PCL), poly-L-lactide (PLLA) and polyurethane (PU) 39 . Autologous cells from the patient are always preferred for seeding the scaffold, as they do not trigger any immune reaction 38 . Cells for tissue-engineering applications can be obtained from MSCs, ESCs, MSCs, iPSCs and other sources 40 .

The polymeric scaffold can be manufactured by a variety of techniques, including 3D printing 39 . The seeded scaffold is exposed to appropriate mechani-cal simulation via the use of mechanical bioreactor which exposes the scaffold to the natural haemody-namic and shear stresses as in vivo. Thereafter, it is implanted into the child 41 .

An exciting new development is the seeding of the ECM of the heart with pluripotent stem cells to de-rive cardiomyocytes with features like automaticity and contractility by Guyette et al. This has opened the possibility of actually ‘manufacturing’ a new heart in the laboratory to be used for transplant 42 .

HEART FAILURE (HF) THERAPIES

VENTRICULAR RESTRAINT THERAPIES

This is a group of therapies aimed at the failing LV, where the goal is to wrap the dilated, failing heart, thereby constraining its end-diastolic dilatation, pre-venting further remodelling. Two devices underwent human trials: The Acorn CorCap, and The Paracor HeartNet, both however, failed to show any signifi -cant clinical advantage 43 , 44 . The QVR concept and its derivatives (VenTouch and BACE devices) are a prom-ising group of therapies aimed at tackling ischaemic MR (see section on ‘Valvular Heart Disease’).

VENTRICULAR ASSIST DEVICES (VADs)

The current crop of devices ( Fig. 95-5 ) is smaller and quieter than earlier-generation devices; they allow

Cell culture

Cellseeding

Passaging

Heart valveIn vitro conditioning

Implantation

Harvest ofautologous

vascular cells

Figure 95-4. Schema of a tissue-engineered heart valve.


for increased exercise capacity, improved functional status and the ability to resume normal activities at home 45 , 46 .

A major controversy is the comparative perfor-mance of continuous fl ow (CF) versus pulsatile fl ow (PF) devices. Currently HeartMate III, a CF device, is being evaluated for paediatric use 47 and CF devices comprise over 98% of LVAD implantations in the USA 48 . Adverse clinical outcomes such as aortic in-suffi ciency, thrombosis, exacerbation of right HF and bleeding remain a signifi cant problem after implantation with CF LVAD 49 . The problem of thrombosis is more vexing in paediatric LVADs ow-ing to the smaller bore tubings. Newer antithrom-botic coatings are being investigated with a view to completely eliminate the need for systemic antico-agulation. Liquid-infused coatings 50 and adherent liquid coatings 51 are two such new technologies. Liquid-infused coatings permeate a porous or roughened surface with an omniphobic liquid (e.g. perfl uorocarbon or silicone). A related adherent liq-uid coating method, tethered liquid perfl uorocar-bon (TLP) coatings, can be used to coat smooth surfaces of existing clinically approved medical de-vices. These developments will eliminate the need for systemic heparinization and its attendant bleed-ing risks in the future.

Other problems with CF devices include RV fail-ure due to rapid LV unloading 52 , and increased inci-dence of GI bleeding 53 . Future innovations, like speed modulation used to create pulsatility in CFVADs, may offer a potential solution to these problems 54 . CF VADs however, have better out-comes than PF devices. Already miniaturized pump-CircuLite Surgical Systems ( Fig. 95-6 ) are available which can be placed in a subcutaneous pacemaker pocket and the VAD can be implanted as an off-pump technique with extubation within the oper-ating suite.

Based on fl ow profi le, CF devices can be classifi ed into:

(a) Axial flow devices, including the HeartAssist 5 (Reliant Heart), Heart Mate II, Heart Mate III, MVAD (Heart Ware) and Jarvik 2000 (Jarvik Heart): They use a propeller to push blood through the device outlet.

(b) Centrifugal flow devices such as the HVAD (HeartWare) and DuraHeart (Terumo): They use blades to revolve blood through the device with advantages of higher flow pulsatility and smaller device size.

The HeartMate III (Thoratec), a centrifugal CF LVAD incorporates these advantages including the option for physiologic pulsatility, a bearingless pump rotor and an accurate flow estimator. The EVAHEART LVAS is a hydraulically levitated cen-trifugal pump that has shown promising results in 118 clinical implants in Japan 55 . Future results from these centrifugal devices may help elucidate

Heartmate170mm × 55mm

1150g

Novacor145mm × 60mm

1000g

DuraHeart73mm × 48mm

540g

Levacor440g

VentrAssist298g

Heart Mate II81mm × 43mm

281g

INCOR120mm × 30mm

200g

HeartAssist5

Older Technology

VAD Size Comparison

New Technology

HVAD145g

92g

Figure 95-5. Evolution of VADs.

Figure 95-6. The CircuLite device, compared with an ‘AA’ battery.


advantages of centrifugal flow over axial flow de-vices, as well as help solve the conundrum of CF versus PF pumps.

The MVAD (HeartWare), although an axial flow pump, incorporates some design elements of cen-trifugal pumps, and has an incredibly low priming volume (5 mL) and 22 mL displacement volume. This marvel of a VAD affords partial or full support with an impeller levitation system and has ultra-thin drive lines and can be used for biventricular support ( Fig. 95-7 ). Future VAD designs will see ‘hy-brids’ like these giving the best of both axial and centrifugal fl ow mechanisms.

The scope of use of VADs will expand with the feasibility of enhanced myocardial recovery follow-ing implantation as ‘bridge to decision’ or even destination therapy along with adjunctive therapies such as pharmacologic or cell-based therapy 56 .

Robotic Silicone Sleeve

This device currently under evaluation in animal models wraps around the ventricle and squeezes it to mimic the contractile action of the myocardium. The robotic sleeve uses compressed air to power silicone muscles that compress the heart and im-prove EF 57 .

EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO)

ECMO is undergoing rapid refi nements, especially with regard to anticoagulation and duration of

support. The future will see an expansion in the scope of indications for use of venoarterial ECMO (VA-ECMO) for cardiac arrest refractory to conven-tional cardiopulmonary resuscitation, in patients considered ‘hopeless cases’ in current times. For this to fructify, the establishment of well-oiled ECMO programmes and teams with appropriate fi nancial support can be envisaged.

AORTA

Aortic pathologies will see a thoracic endovascular aortic repair (TEVAR) solution. Hybrid technologies and frozen elephant trunk surgeries will become routine and commonplace. Although descending aortic TEVAR options are standardized now, ascend-ing aorta and arch TEVAR options too will emerge in the future. One would like to have total endovas-cular solution, with a composite of TEVAR and TAVR, in patients of type I aortic dissection with severe AR.

GENE THERAPY IN CARDIAC SURGERY

Cardiac gene transfer received an impetus in 1990s with the direct surgical intramyocardial injection of �-galactosidase/plasmid DNA construct into the LV of beating rat hearts. Gene expression was demonstrated in myocytes 4 weeks after delivery 58 . Cardiovascular applications currently account for 7.8% of gene ther-apy clinical trials, and cardiac surgery accounts for only 6.2% of these – or 0.48% of all gene therapy clinical trials 59 .

MVAD®Pumpwith hybrid impeller technology

Gimbaled Sewing Ringwith depth and angle adjustability

PALTM Patient Peripheralswith integrated controller &battery system

qPulseTM Cyclewith patient customization

Figure 95-7. The MVAD device.


Most trials of gene therapy in cardiac surgery have pertained to stimulation of angiogenic growth factors. On completion of CABG, vascular endothe-lial growth factor (VEGF) has been administered by direct myocardial injection into the areas of scarred myocardium that demonstrated reversible ischaemia on perfusion scan 60 . There was improvement in an-gina class as well as regional improvements in ven-tricular function 61 . Gene therapy will emerge as a useful adjuvant therapy to CABG, especially in de-ranged LV function, in times to come.

AVOIDING REJECTION – IMMUNOSUPPRESSION

Another promising fi eld for gene therapy is immu-nosuppression following heart transplant. Gene ad-ministration into the donor organ may be carried out ex vivo in an effort to ‘turn off’ the immune response associated with rejection 14 . Gene therapy is also being looked at with a view to enhance the patency of venous conduits in CABG as explained in the section on ‘Conduits’ in CAD.

PAEDIATRIC CARDIAC SURGERY

ROBOTICS AND IMAGING 62

Beating heart intracardiac image-guided robotic surgery is being evaluated for procedures like ASD, VSD or MV repairs, without the use of CPB. The procedures are done with real-time 3D echocar-diography and video-assisted cardioscopy for proper visualization. Concentric tube robots are being developed for use, especially in minimally invasive procedures in paediatric patients given the very limited operating space available. Real time image fusion of 3D echocardiographic and magnetic resonance imaging (MRI)/cineangio-graphic images would give greater clarity during such procedures.

FETAL CARDIAC SURGERY 63

Intrauterine balloon aortic/pulmonary valvulo-plasty, prenatal intervention on the atrial septum and fetal cardiac pacing are some catheter-based interventions currently being practised on the un-born fetus. These are mainly for alleviation of con-ditions like hypoplastic left heart syndrome, con-genital aortic/pulmonary stenosis and congenital heart block.

Advances in fetal CPB techniques in the future will facilitate a robotic interventional, open-heart

approach, with every attempt to restore the heart to a two-ventricular physiology.

There shall also be a sea change in the manage-ment of right ventricular obstruction, especially with the availability of tissue-engineered conduits and valves and percutaneous techniques for their deployment. Management of Eisenmenger syn-drome, either by use of genetically engineered or-gans to replace the damaged heart and the lungs or by conservative techniques of deloading and rest-ing the heart will fi nd more wide applications. Availability of pericardial patch substitutes in form of porous, elastic and biodegradable materials, like polyester and polyurethane urea, (a bioabsorbable gelatin sheet latticed with polyglycolic acid) that would facilitate cellular ingrowth during healing process, are going to make redo surgeries simpler and easier.

MISCELLANEOUS ISSUES

ROBOTICS

The newest generation da Vinci robotic system with an additional telemanipulated arm and an endostabilizer has greatly enhanced the scope of robotics. Future robotic systems will incorporate strain sensors to the instrument arms, allowing for haptic and tactile feedback and precise control of force. We are going to see virtual immobilization using gated instruments, allowing for more opera-tive options and improved dexterity 7 . Also instead of sutures being used, we are going to see sealants and connectors being developed. Instrument and camera sizes will decrease, and optics will improve, allowing for smaller incisions. In future, it should be possible to carry out remote, robotically con-trolled surgeries (Telerobotics).

Nanotechnology and micro-electromechanical systems (MEMS), microprocessors with microsen-sors that have complex sensory and reactive mecha-nisms, supported by augmented virtual reality sys-tems using 3D images from MRI, positron emission tomography (PET) or computed tomographic (CT) scans are likely to make these surgical procedures, not only commonplace but an essential part of an average surgeon’s domain.

CPB AND INTENSIVE CARE

Advances in CPB and myocardial protection with development of miniaturized and biocompatible circuits to avoid platelet and complement activa-tion are going to make these surgeries patient and


physician friendly. Computerized management us-ing artifi cial intelligence, sterility techniques, fl uid management, antibiotics, ionotropes and blood transfusion medicine and component therapy are further going to make surgery safer. Computers too, both for analysing and predicting results and for mathematical modelling for research, are fi nding their applications in cardiac surgery. With minimi-zation and miniaturization of surgery, both day care and domiciliary surgery is going to become the or-der of the day.

IMAGING

Developments in ancillary specialities are going to be to the advantage of cardiac surgeons, especially in imaging. Advances in CT-based delineation of coronary anatomy, composition and characteriza-tion of atherosclerotic plaques, identifi cation of hi-bernating myocardium, assessment of myocardial function and intracardiac volumes and dimensions, identifi cation of intracardiac shunts and detailed cardiovascular anatomy delineation, using nonin-vasive techniques (specially for aortic dissection), developments in the fi eld of MRI, newer modalities in form of 3D and 4D cardiac echocardiography, fetal ECG, ultrasound and magnetocardiography are all going to be revolutionary and in some cases, disruptive.

GUIDELINES AND TRAINING

Besides scientifi c issues in cardiac surgery, training issues will also assume importance in the future. Catheter-based training in conjunction with cardi-ologists, and the use of app- and simulator-based training will be seen. Therefore, more importance will be laid on a collaborative approach to training, in consonance with the heart team concept, thereby fostering more collegiality with our cardiology col-leagues. Opportunities will also have to be created for externships at various centres of excellence and adequate exposure to experimental and core re-search. Such a step would have to be coupled with a change in the curriculum of training in cardiac surgery. This would also help in addressing the dwindling numbers of cardiac surgeons. In fact, there is an estimated 46% increased demand for cardiac surgeons by 2025 (see ref 64 ).

As far as India is concerned, another major issue is the absence of customized indigenous guide-lines. Equally important is the creation of a ‘Na-tional Registry’ of cardiac surgery which would include disease incidence, results and audits. As a

push towards transparency, these data should be freely available in the public domain, and could form the basis of regulation and good governance besides registration in state/national medical councils.

RESEARCH AND INNOVATIONS

Sophisticated research techniques, especially with a view to study the heart valve function, like micro-scopic fl ow analysis, computational fl uid dynamic modelling, laser Doppler velocimetry, high inten-sity transit signals and mathematical modelling are going to make newer technique developments much easier and rewarding.

GENDER AND PERSONNEL ISSUES

These too shall merit bigger attention going for-wards. Cardiac surgery is a male-dominated fi eld with only a few women holding the fort for the fair sex. The future will see more women enter this fi eld as they progressively conquer other, tra-ditionally male-dominated areas. Another major problem is early burnout due to long work hours and fi nancial issues. These will have to be ad-dressed by professional bodies by putting pressure on governments.

CONCLUSION

Cardiac surgery is moving towards a minimally in-vasive approach and miniaturization with conser-vation and respect for natural elements (ablation over excision). Thus, reparative valve surgery and small pump VADs along with minimally invasive techniques, using image guidance rather than di-rect vision, will be the future. We are going to see endovascular approach, with access through blood vessels rather than incisions. Aortic disorders and most forms of valve pathologies will be handled through transcatheter approaches using sutureless technologies. There will also be greater stress laid on transparency with public reporting of results and outcomes and on quality initiatives like infec-tion rates. Total arterial grafting for CABG will be-come a quality matrix for surgeon certifi cation. Also, as transcatheter technology develops further, operations are going to get more complex in nature and simpler lesions will fall in the purview of PCIs and will be handled by the cardiologists. This, coupled with an estimated 46% increased demand for cardiac surgeons by 2025, bodes a challenging but bright future for cardiac surgery and cardiac sci-ences in general.


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chapter 95 · chapter 95 future directions in cardiac surgery o.p. yadava † kundu currently less...

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